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Levisticum officinale extract protects against CCl4-induced hepatotoxicity through anti-inflammatory,anti-fibrotic,and antioxidant properties in rats
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作者 Nahid Ghaedi Iran Pouraboli +1 位作者 Mansour Mirtadzadini Mohammad-mehdi Moeini-aghtaie 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2024年第8期331-340,共10页
Objective:To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced hepatotoxicity.Methods:Different doses of Levisticum officinale extract were given orally to rats for 10 days,then... Objective:To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced hepatotoxicity.Methods:Different doses of Levisticum officinale extract were given orally to rats for 10 days,then rats received a single dose of CCl4(2.5 mL/kg,50%v/v in liquid paraffin).Biochemical and histopathological assays were performed to assess the effects of the extract on liver function and architecture.Moreover,antioxidant and oxidative markers as well as inflammatory and fibrotic indicators were measured.Results:Pretreatment with Levisticum officinale extract significantly mitigated CCl4-induced damage to liver structure,improved serum levels of alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,urea,total bilirubin,and total protein,enhanced glutathione content and superoxide dismutase and catalase activities in the liver,as well as decreased plasma and hepatic malondialdehyde levels.Immunohistochemical results demonstrated that the extract reduced Ki-67 andα-SMA expression and Masson’s trichrome staining revealed decreased liver collagen in rats treated with Levisticum officinale extract.Moreover,Levisticum officinale extract markedly decreased the gene expressions of TNF-α,IL-6,TGF-β1,MCP-1,and COX-2.Conclusions:Levisticum officinale extract exerts hepatoprotective effects on CCl4-induced hepatotoxicity through antioxidant,anti-inflammatory,and anti-fibrotic activities. 展开更多
关键词 Levisticum officinale ccl4 Inflammation Liver toxicity ANTIOXIDANT
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Antioxidant activity and hepatoprotective effect of 10 medicinal herbs on CCl4-induced liver injury in mice 被引量:3
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作者 Xiao Meng Guo-Yi Tang +3 位作者 Pin-He Liu Chan-Juan Zhao Qing Liu Hua-Bin Li 《World Journal of Gastroenterology》 SCIE CAS 2020年第37期5629-5645,共17页
BACKGROUND Many natural products confer health benefits against diverse diseases through their antioxidant activities.Carbon tetrachloride(CCl4)is often used in animal experiments to study the effects of substances on... BACKGROUND Many natural products confer health benefits against diverse diseases through their antioxidant activities.Carbon tetrachloride(CCl4)is often used in animal experiments to study the effects of substances on liver injury and the related mechanisms of action,among which oxidative stress is a major pathogenic factor.AIM To compare antioxidant and hepatoprotective activities of ten herbs and identify and quantify phytochemicals for the one with strongest hepatoprotection.METHODS The antioxidant activity of ten medicinal herbs was determined by both ferricreducing antioxidant power and Trolox equivalent antioxidant capacity assays.The total phenolic and flavonoid contents were determined by Folin–Ciocalteu method and aluminum chloride colorimetry,respectively.Their effects on CCl4-induced oxidative liver injury were evaluated and compared in a mouse model by administrating each water extract(0.15 g/mL,10 mL/kg)once per day for seven consecutive days and a dose of CCl4 solution in olive oil(8%,v/v,10 mL/kg).The herb with the strongest hepatoprotective performance was analyzed for the detailed bioactive components by using high-performance liquid chromatography-electrospray ionization source-ion trap tandem mass spectrometry.RESULTS The results revealed that all tested herbs attenuated CCl4-induced oxidative liver injury;each resulted in significant decreases in levels of serum alanine transaminase,aspartate transaminase,alkaline phosphatase,and triacylglycerols.In addition,most herbs restored hepatic superoxide dismutase and catalase activities,glutathione levels,and reduced malondialdehyde levels.Sanguisorba officinalis(S.officinalis)L.,Coptis chinensis Franch.,and Pueraria lobata(Willd.)Ohwi root were the three most effective herbs,and S.officinalis L.exhibited the strongest hepatoprotective effect.Nine active components were identified in S.officinalis L.Gallic acid and(+)-catechin were quantified(7.86±0.45 mg/g and 8.19±0.57 mg/g dried weight,respectively).Furthermore,the tested herbs displayed a range of in vitro antioxidant activities proportional to their phenolic content;the strongest activities were also found for S.officinalis L.CONCLUSION This study is of value to assist the selection of more effective natural products for direct consumption and the development of nutraceuticals or therapeutics to manage oxidative stress-related diseases. 展开更多
关键词 Antioxidant activity ccl4-induced liver injury Medicinal herbs HEPATOPROTECTION Sanguisorba officinalis L. Coptis chinensis Franch
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Protective effects of NYG-1 on CCl4-induced acute liver injury in rats
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作者 Hong-liangLI Xuan-binWANG +2 位作者 MingLIU Yi-binFENG Qiu-fangZHANG 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2015年第S1期59-59,共1页
OBJECTIVE To study the protection effects and mechanisms of NYG-1 on CCl4-induced acute liver injury.METHODS Acute liver injury model of rats was established by using CCl4.48 male SPF SD rats were weighed and randomly... OBJECTIVE To study the protection effects and mechanisms of NYG-1 on CCl4-induced acute liver injury.METHODS Acute liver injury model of rats was established by using CCl4.48 male SPF SD rats were weighed and randomly divided into six groups with 8 in each group,normal group,model group,positive control group(silibinin),low-,medium-and high-dose NYG-1 group.Silibinin was given orally to rats in the positive control group,NYG-1(high-,medium-and low-dose)was given orally in the high-,medium-and low-dose NYG-1group,respectively.Those rats were administered appropriately according to the group once daily for seven consecutive days.On the seventh day,rats were treated with 10% CCl4(10mL·kg-1 of0.1% CCl4 solution in olive oil)intraperitoneally injecting(ip)to induce acute liver injury,except the normal group.At 16 h after CCl4 treatment,rats were weighed,then anaesthed with ether,the blood and liver were collected.Serum ALT,AST,LDH and ALP were measured.MDA content and SOD activity in liver homogenate were detected.The histopathological changes of liver were observed by H&E staining.RESULTS Acute liver injury model was established successfully in rats by intraperitoneally injecting CCl4.Pretreatment with medium and high dose NYG-1 decreased the increase of ALT,AST and MDA induced by CCl4,but it had no influence on serum LDH,ALP level and SOD activity in the liver homogenate.CONCLUSION The obtained results suggest that oral administration of NYG-1 hasve the protective effects against CCl4-induced acute hepatic injury in rats,Its mechanism may be related to antioxidant-like action. 展开更多
关键词 NYG-1 ccl4 ACUTE LIVER INJURY
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Ablation of apoptosis-stimulating of p53 protein 1 protects mice from acute hepatic injury and dysfunction via NF-κB pathway in CCl4-induced hepatotoxicity
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作者 Tolessa Muleta Daba Xiang Huang +8 位作者 Timur Yagudin Ying Yang Jiangang Wang Xiaoyu Fu Yue Zhao Haiyu Gao Yang Zhou Zhenwei Pan Xiangyu Zhong 《Frigid Zone Medicine》 2021年第1期53-64,共12页
Acute liver injury(ALI)is characterized by apoptosis,inflammation,and oxidative stress,and pathogenic mechanism of ALI is poorly understood.Apoptosis-stimulating of p53 protein 1(ASPP1)is involved in environmental res... Acute liver injury(ALI)is characterized by apoptosis,inflammation,and oxidative stress,and pathogenic mechanism of ALI is poorly understood.Apoptosis-stimulating of p53 protein 1(ASPP1)is involved in environmental responses,tumor growth,and NF-κB activity,which is of critical importance to ALI.However,the role of ASPP1 in ALI remains largely unexplored.The current study aimed to determine the role of ASPP1 in ALI induced by CCl4 and the underlying mechanism.ASPP1 expression was detected in wild type(WT)mice with ALI induced by CCl4.The function of ASPP1 in ALI induced by CCl4 was investigated using conventional knockout ASPP1 mice.ASPP1 expression significantly increased in ALI mice at 24 hours after CCl4 injection.Deletion of ASSP1 ameliorated apoptosis,inflammation,and necrosis in ALI relative to WT mice.In addition,deficiency of ASPP1 improved liver flood flow as well as ALT and AST levels.The levels of phosphorylated p65 and phosphorylated IκBαwere lower in ASPP1-/-mice than in WT mice with ALI.These results implicate that deletion of ASPP1 may act via inhibition of the NF-кB pathway and protect mice from ALI,which may be a new potential therapeutic target for the treatment of ALI. 展开更多
关键词 APOPTOSIS ASPP1 ccl4 Liver injury INFLAMMATION NF-ΚB
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Portulaca oleracea alleviates CCl4-induced acute liver injury by regulating hepatic S100A8 and S100A9 被引量:2
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作者 Aruna Qian Lu Zhou +2 位作者 Dongxu Shi Zongran Pang Binan Lu 《Chinese Herbal Medicines》 CAS 2023年第1期110-116,共7页
Objective: Acute liver injury(ALF) is a potential factor of many serious hepatopathies. Carbon tetrachloride(CCl4) is a possible environmental toxicant that can induce ALF. Portulaca oleracea(PO) is one of the most po... Objective: Acute liver injury(ALF) is a potential factor of many serious hepatopathies. Carbon tetrachloride(CCl4) is a possible environmental toxicant that can induce ALF. Portulaca oleracea(PO) is one of the most popular edible herbs and has several biological activities such as antioxidant, antimicrobial, antiinflammatory effects. We explored the significance of PO in regulating inflammatory function in animal models and cultured hepatocytes during liver damage caused by CCl4.Methods: The effect of PO on ALF was evaluated by CCl4-induced mice models in vivo. Hepatic levels of transaminase activities and inflammatory factors were examined. The gene and protein expression of S100A8 and S100A9 were measured by RT-PCR and Western blot analysis. Meanwhile, the efficacy of PO was certified by HepG2 cells in vitro. The transaminase activities, inflammatory factors, and the protein expression of S100A8 and S100A9 were also detected.Results: Animal tests showed that pretreatment with PO reduced the liver pathological tissue damage and the serum levels of ALT, AST, ALT and LDH, as well as reducing the pro-inflammatory cytokines(IL-1β, IL-6, TNF-a) secretion in CCl4-induced liver injury mice. Simultaneously, Hep G2 cells pretreated with PO exhibited a significant decrease in the activities of ALT and AST. Moreover, PO resulted in a significant downregulation of the pro-inflammatory markers S100A8, S100A9 gene and protein expression on CCl4induced acute liver injury was demonstrated entirely in vivo and vitro experiments.Conclusion: PO may down-regulate S100A8 and S100A9 and inhibit pro-inflammatory cytokines’ release,indicating a potential clinical effect for controlling the disease. 展开更多
关键词 acute liver injury ccl4 Portulaca oleracea L. S100A8 S100A9
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CCL4在肿瘤微环境中影响免疫逃逸的研究进展
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作者 陈然 杨新月 +2 位作者 刘倩 张树才 马丽 《中国肺癌杂志》 CAS CSCD 北大核心 2024年第8期613-621,共9页
免疫治疗已成为当下恶性肿瘤治疗的基石。然而,不同患者对免疫治疗的反应具有较大异质性,并非都能从中获益。当下亟需寻找能高效预测免疫治疗疗效的生物标志物。C-C趋化因子配体4(C-C chemokine ligand4,CCL4)是一种细胞因子,隶属于炎症... 免疫治疗已成为当下恶性肿瘤治疗的基石。然而,不同患者对免疫治疗的反应具有较大异质性,并非都能从中获益。当下亟需寻找能高效预测免疫治疗疗效的生物标志物。C-C趋化因子配体4(C-C chemokine ligand4,CCL4)是一种细胞因子,隶属于炎症性CCL亚家族,主要由免疫细胞、肿瘤细胞分泌,在正常组织中不表达或者弱表达,在多种恶性肿瘤组织中异常高表达。CCL4与其受体C-C趋化因子受体5(C-C chemokine receptor type 5,CCR5)结合后可招募并介导免疫细胞迁移,破坏肿瘤微环境(tumor microenvironment,TME)的稳定性,参与致癌并促进肿瘤发展。在肿瘤免疫微环境中,CCL4可介导并募集单核细胞、巨噬细胞、自然杀伤(natural killer,NK)细胞、T细胞等关键免疫细胞定向迁移,成为影响免疫治疗疗效的潜在重要元素,而具有特定的价值。本文就CCL4在TME中影响免疫逃逸的研究进展进行综述,以期为基础研究及临床诊疗提供线索和参考。 展开更多
关键词 ccl4 免疫治疗 肿瘤微环境 免疫应答 免疫逃逸
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Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl_4-induced chronic liver damage in rats 被引量:3
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作者 Yun-Kyoung Yim Hyun Lee +4 位作者 Kwon-Eui Hong Young-Il Kim Byung-Ryul Lee Tae-Han Kim Ji-Young Yi 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第14期2245-2249,共5页
AIM: To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats. METHODS: Rats were injected intraperitoneally with CCh (1 mL/kg) and tre... AIM: To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats. METHODS: Rats were injected intraperitoneally with CCh (1 mL/kg) and treated with manual acupuncture using reinforcing manipulation techniques at left GB34 (Yanglingquan) 3 times a week for 10 wk. A nonacupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index, biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted. RESULTS: Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes. CONCLUSION: Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCh-intoxicated rats. 展开更多
关键词 Manual acupuncture Yanglingquan (GB34 ccl4-induced liver damage Hepatoprotective effect
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CCL 4与BDL致大鼠肝损伤中α-SMA、Hab18G/CD147表达的差异
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作者 位小杰 薛超 +1 位作者 史文哲 张聚丹 《黑龙江科学》 2024年第12期120-122,共3页
探究CCL 4腹腔注射和胆总管结扎(Bile Duct Ligation,BDL)致大鼠肝损伤中α-SMA、Hab18G/CD147表达的差异,为法医学鉴定药物性肝损伤提供科学参考。选取雄性SD大鼠60只,随机分为CCL 4对照组(N)、BDL对照组(S)、CCL 4肝损伤组(C)、BDL肝... 探究CCL 4腹腔注射和胆总管结扎(Bile Duct Ligation,BDL)致大鼠肝损伤中α-SMA、Hab18G/CD147表达的差异,为法医学鉴定药物性肝损伤提供科学参考。选取雄性SD大鼠60只,随机分为CCL 4对照组(N)、BDL对照组(S)、CCL 4肝损伤组(C)、BDL肝损伤组(B),每组各15只。各组分别在实验1 w、3 w、5 w时断颈处死5只大鼠,采血检测谷丙转氨酶(Glutamic pyruvic transaminase,ALT)、谷草转氨酶(Aspertate aminotransferase,AST),总胆红素(Total bilirubin,TBIL)、直接胆红素(Direct bilirubin,DBIL),检测α-SMA、Hab18G/CD147mRNA的表达情况。qRT-PCR检测结果显示,C组α-SMAmRNA、Hab18G/CD147mRNA的表达量在1 w、3 w、5 w同时间段相比均高于B组(P<0.05)。与对照组相比较,C组、B组血清中ALT、AST、DBIL、TBIL含量均增加,说明大鼠肝脏均有不同程度的损伤;CCL 4与BDL肝损伤有不同特点,在肝损伤过程中α-SMA、Hab18G/CD147mRNA的表达随着损伤时间的延长表达量逐渐增加。 展开更多
关键词 大鼠肝损伤 ccl 4 BDL Α-SMA HAB18G/CD147
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丙泊酚减弱CCL4诱导脑微血管内皮细胞促炎和细胞毒作用机制研究
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作者 赵娟 龚葛松 《国际检验医学杂志》 CAS 2024年第8期996-1000,共5页
目的 探讨趋化因子配体4(CCL4)诱导脑微血管内皮细胞炎症和细胞毒作用,以及丙泊酚对CCL4诱导效应的拮抗作用。方法 将体外永生化人脑微血管内皮细胞hCMEC/D3分为为对照组、CCL4组、丙泊酚+CCL4组细胞。采用CCK-8试验检测各组细胞增殖活... 目的 探讨趋化因子配体4(CCL4)诱导脑微血管内皮细胞炎症和细胞毒作用,以及丙泊酚对CCL4诱导效应的拮抗作用。方法 将体外永生化人脑微血管内皮细胞hCMEC/D3分为为对照组、CCL4组、丙泊酚+CCL4组细胞。采用CCK-8试验检测各组细胞增殖活力,细胞克隆形成实验分析细胞克隆形成能力,流式细胞术Annexin V/PI双染检测细胞凋亡情况。采用实时荧光定量PCR(qPCR)检测细胞细胞炎症基因、血栓形成相关基因的表达情况,酶活性检测试剂盒检测环氧化酶-2(COX-2)及凝血酶活性。结果 与对照组细胞比较,CCL4组细胞增殖活力显著减弱,细胞克隆形成能力减低,凋亡细胞增加,差异有统计学意义(P<0.001);与CCL4组,丙泊酚+CCL4组细胞增殖活力显著上调,细胞克隆形成能力增加,凋亡细胞减少,差异有统计学意义(P<0.001)。qPCR检测结果显示,与对照组比较,CCL4组炎症相关基因白细胞介素(IL)-1β、IL-6、IL-8、核转录因子κB(NF-κB)、肿瘤坏死因子α(TNF-α)及COX-2基因表达上调,血栓形成基因Thrombin、Factor 8、VWF及TXA表达增加,COX-2酶及凝血酶活性增加,差异有统计学意义(P<0.001)。丙泊酚可明显抑制CCL4对hCMEC/D3的炎症相关基因及血栓形成基因的促进表达作用,以及CCL4对hCMEC/D3的COX2酶及凝血酶活性。结论 丙泊酚可减轻CCL4对脑微血管内皮细胞的细胞毒作用,并拮抗其促炎和促血栓形成基因表达。 展开更多
关键词 ccl4 丙泊酚 人脑微血管内皮细胞 细胞增殖 凋亡 炎症 血栓
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Hepatoprotective and antioxidant effects of baicalin against CCl4-induced hepatotoxicity 被引量:8
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作者 Song Liu Xiaohui Lv +1 位作者 Zongxi Sun Ruiqiang Su 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2015年第8期538-544,共7页
Scutellaria baicalensis is widely cultivated in eastern Asia, particularly in China. In the present study, we isolated baicalin from this plant and studied for its hepatoprotective activity against CCl4-induced oxidat... Scutellaria baicalensis is widely cultivated in eastern Asia, particularly in China. In the present study, we isolated baicalin from this plant and studied for its hepatoprotective activity against CCl4-induced oxidative damage in rats. Our findings revealed that baicalin exhibited strong antioxidant activity in vitro. In established in vivo tests, baicalin showed effective protective effects by reducing the elevated levels of glutamate pyruvate transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB) and malondialdehyde (MDA) against CCl4-induced damage, and it restored the activities antioxidant defense substances, such as superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH), toward their normal levels. These data were supplemented with histopathological examination of rat liver sections. The results demonstrated that baicalin could be proposed to protect the liver against CCh-induced oxidative damage in rats, and the possible underlying mechanism of the activity could be due to its free radical-scavenging and antioxidant activity. 展开更多
关键词 BAICALIN HEPATOPROTECTIVE ccl4 ANTIOXIDANT
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Estrogen reduces CCL_4-induced liver fibrosis in rats 被引量:14
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作者 Jun-Wang Xu Jun Gong +5 位作者 Xin-Ming Chang Jin-Yan Luo Lei Dong Zhi-Ming Hao Ai Jia Gui-Ping Xu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2002年第5期883-887,共5页
AIM: Chronic liver diseases, such as fibrosis or cirrhosis,are more common in men than in women. This genderdifference may be related to the effects of sex hormones onthe liver. The aim of the present work was to inve... AIM: Chronic liver diseases, such as fibrosis or cirrhosis,are more common in men than in women. This genderdifference may be related to the effects of sex hormones onthe liver. The aim of the present work was to investigatethe effects of estrogen on CCL4-induced fibrosis of the liverin rats.METHODS: Liver fibrosis was induced in male, female andovariectomized rats by CCL4 administration. All the groupswere treated with estradiol(1 mg/kg) twice weekly. Andtamoxifen wasgiven to male fibrosis model. At the end of 8weeks, all therats were killed to study serum indicators andthe livers.RESULTS: Estradiol treatment reduced aspartateaminotransferase(AST), alanine aminotransferase (ALT),hyaluronic acid(HA) and type IV collagen(CIV) in sera,suppressed hepatic collagen content, decreased the areas ofhepatic stellate cells (HSC) positive for α-smooth muscle actin(α-SMA), and lowered the synthesis of hepatic type I collagensignificantly in both sexes and ovariectomy fibrotic rats inducedby CCL4 administration. Whereas, tamoxifen had the oppositeeffect. The fibrotic response of the female liver to CCL4treatment was significantly weaker than that of male liver.CONCLUSION: Estradiol reduces CCL4-induced hepaticfibrosis in rats. The antifibrogenic role of estrogen in theliver may be one reason for the sex associated differencesin the progression from hepatic fibrosis to cirrhosis. 展开更多
关键词 雌激素 大鼠 肝纤维化 ccl4 慢性肝病 作用机制
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小分子多肽LK-5对CCl4致急性肝损伤小鼠的保护作用研究 被引量:2
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作者 陈俊 廖彭莹 +3 位作者 张新锐 黄秀欢 杨宇静 刘华宇 《中国畜牧兽医》 CAS CSCD 北大核心 2023年第9期3833-3841,共9页
【目的】研究小分子多肽LK-5(氨基酸序列为LHMFK)对CCl4致急性肝损伤模型小鼠的保护作用,探讨其作用机制。【方法】72只小鼠随机分为正常组、模型组、联苯双酯组(150 mg/kg)及LK-5低、中、高剂量组(30、60、120 mg/kg),每组12只。连续给... 【目的】研究小分子多肽LK-5(氨基酸序列为LHMFK)对CCl4致急性肝损伤模型小鼠的保护作用,探讨其作用机制。【方法】72只小鼠随机分为正常组、模型组、联苯双酯组(150 mg/kg)及LK-5低、中、高剂量组(30、60、120 mg/kg),每组12只。连续给药10 d, 1次/d,每次10 mL/kg。末次给药2 h后,各组(除正常组外)腹腔注射0.1%CCl4花生油溶液,建立CCl4致小鼠急性肝损伤模型,16 h后,按照试剂盒方法,检测小鼠血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、总胆汁酸(TBA)和碱性磷酸酶(AKP)水平,检测肝脏超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、肿瘤坏死因子(TNF-α)、白细胞介素-6(IL-6)、IL-10、血管紧张素1-7(Ang 1-7)和血管紧张素Ⅱ(AngⅡ)水平。制作肝脏病理组织切片,苏木精-伊红染色(HE)后观察肝脏组织病理学变化。【结果】与正常组比较,模型组小鼠肝细胞有明显的脂肪变性,炎细胞分散分布于肝小叶血管周围和肝实质内,血清ALT、AST、AKP活性和TBA水平均显著上升,肝组织SOD、GSH-Px活性显著下降,MDA水平显著上升(P<0.05),说明成功建立急性肝损伤模型,TNF-α、IL-6、AngⅡ水平显著升高(P<0.05)。与模型组比较,LK-5中、高剂量组能够显著降低血清ALT、AST活性(P<0.05),各剂量组均可降低血清TBA水平和AKP活性(P<0.05),LK-5高剂量组能够显著提高小鼠肝组织SOD、GSH-Px活性(P<0.05),LK-5中、高剂量组能够显著降低肝组织MDA水平(P<0.05),LK-5高剂量组TNF-α水平显著降低(P<0.05),各剂量组能够显著降低肝组织IL-6、AngⅡ水平(P<0.05)。病理切片结果显示,LK-5各剂量组炎细胞均有不同程度减少,LK-5高剂量组肝小叶血管周围和肝实质内无炎细胞浸润。【结论】LK-5各剂量组对CCl4致急性肝损伤小鼠具有保护作用,其中60、120 mg/kg LK-5效果更为明显,其作用机制可能与抗氧化、抗炎及对肾素-血管紧张素系统(RAS)的调控有关。 展开更多
关键词 小分子多肽LK-5 ccl4 急性肝损伤 保护作用
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Prevention of Carbon Tetrachloride (CCl4)-Induced Liver Damage in Guinea Pigs by Cyphostemma digitatum
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作者 Mohamed A. Al-Duais Yahya S. Al-Awthan +1 位作者 Abdulbaset Al-Mashad Mukhtar A. Shamsan 《Journal of Life Sciences》 2012年第2期137-143,共7页
Cyphostemma digitatum (Vitaceae) is a perennial, climbing, succulent undershrub with compound fleshy leaves and tendrils. The plant is used mainly as a food flavoring, but it is also a main constituent of traditiona... Cyphostemma digitatum (Vitaceae) is a perennial, climbing, succulent undershrub with compound fleshy leaves and tendrils. The plant is used mainly as a food flavoring, but it is also a main constituent of traditional Yemeni soup (Marak). Besides that, it has been described to be used as a medicinal plant. The aim of this work was to study the hepatoprotective effect of the aqueous extract of C. digitatum against CCl4-induced liver injury in Guinea pigs. Animals were divided into four groups. Group I, served as normal control. Group II received 2 mL CCl4/kg b.w. diluted with olive oil, at 1:1 ratio on day 11. Group III (test group) was pre-treated orally with 100 mg/kg b.w. aqueous leaves extract of C. digitatum for 10 days followed by subcutaneous injection of CC14 (2 mL/kg b.w.), once on day 11. Group IV were orally given Liv-52 (100 mg/kg b.w.) once daily for 10 days followed by subcutaneous injection of CC14. Our results show that, the activity of serum hepatic enzymes (alanine aminotranferase (ALT), aspartate aminotranferase (AST), and alkaline phosphatase (ALP)) were significantly elevated in Guinea pigs treated with CCl4, while both the C. digitatum extract and Liv-52 reduced significantly these enzymes activity. Also, the levels of glucose, urea, cholesterol and triglycerides were decreased when compared with intoxicated control. Histopathological examination of intoxicated animals showed fatty changes, inflammation and necrosis indicating liver damage, while the animals received C. digitatum or Liv-52 showed less pathological effects or normal liver when compared to animals treated with CC14 alone. Biochemical and histological results confirm the hepatoprotective effect of aqueous extract of C. digitatum. 展开更多
关键词 Cyphostemma digitatum extract ccl4 liver damage Guinea pig.
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The new antioxidant 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2- dihydroquinoline has a protective effect against carbon tetrachloride-induced hepatic injury in rats
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作者 Evgenii Dmitrievich Kryl'skii Darya Andreevna Sinitsyna +4 位作者 Tatyana Nikolaevna Popova Khidmet Safarovich Shikhaliev Svetlana Mikhajlovna Medvedeva Larisa Vladimirovna Matasova Valentina Olegovna Mittova 《The Journal of Biomedical Research》 CAS CSCD 2022年第6期423-434,共12页
Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have ant... Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have antioxidant activity,are of interest.We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.Here,we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline(BHDQ)for carbon tetrachloride(CCl4)-induced liver injury in rats.Results suggested that BHDQ normalized the alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transpeptidase in serum.We also observed an improvement in liver tissue morphology related to BHDQ.Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with CCl4-induced liver injury.BHDQ promoted activation changes in superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,and glutathione transferase on control values in animals with CCl4-induced liver injury.BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and forkhead box protein O1 factors.Therefore,the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue,through antioxidation. 展开更多
关键词 ccl4-induced hepatic injury oxidative stress 1-benzoyl-6-hydroxy-2 2 4-trimethyl-1 2-dihydroquinoline antioxidants
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壮方壮肝逐瘀煎联合骨髓间充质干细胞移植对CCl4大鼠肝纤维化的影响 被引量:3
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作者 罗艺徽 吴姗姗 +1 位作者 王振常 吕艳杭 《湖南中医药大学学报》 CAS 2023年第3期443-449,共7页
目的 探讨壮肝逐瘀煎联合骨髓间充质干细胞(bone marrow mensenchymal stem cell,BMMSC)移植对CCl4诱导的肝纤维化大鼠的影响。方法 取20只大鼠为正常对照组(A组),另取80只造模成功后的大鼠,随机分为模型组(B组)、单纯壮肝逐瘀煎组(C组... 目的 探讨壮肝逐瘀煎联合骨髓间充质干细胞(bone marrow mensenchymal stem cell,BMMSC)移植对CCl4诱导的肝纤维化大鼠的影响。方法 取20只大鼠为正常对照组(A组),另取80只造模成功后的大鼠,随机分为模型组(B组)、单纯壮肝逐瘀煎组(C组)、单纯BMMSC组(D组)、壮肝逐瘀煎联合BMMSC组(E组),每组20只。A组、B组、D组灌服生理盐水(0.1 m L/kg,1次/d),C组、E组灌服壮肝逐瘀煎(0.1 mL/kg,1次/d),各组均连续干预12周。其中,第4周末,B组、C组尾静脉注射生理盐水,D组、E组尾静脉注射BMMSC。干预后,采用HE染色观察各组大鼠肝脏病理变化;采用全自动生化仪检测肝功能指标[谷草转氨酶(aspartate aminotransaminase,AST)、谷丙转氨酶(alanine aminotransferase,ALT)、总胆红素(total bilirubin,TBIL)、白蛋白(albumin,ALB)]变化;采用RT-PCR检测肝组织甲胎蛋白(alpha fetoprotein,AFP)、ALB、细胞角蛋白18(cytokeratin 18,CK18)mRNA;采用Western blot检测表皮生长因子(epidermal growth factor,EGF)、肝细胞生长因子(hepatocyte growth factor,HGF)的表达;冷冻切片技术检测携带绿色荧光蛋白的BMMSC向肝脏归巢的情况。结果 B组肝小叶结构被广泛增生的纤维化组织分割并包绕成大小不等的圆形或类圆形的肝细胞团(即假小叶),肝细胞排列絮乱、坏死、变性及再生。C组、D组、E组肝小叶结构得到不同程度的恢复,肝细胞变性、水肿得到不同程度的改善。与A组比较,B组AST、ALT、TBIL明显升高(P<0.05),ALB和AFP、ALB、CK18 m RNA及HGF、EGF蛋白表达明显降低(P<0.05)。与B组比较,C组、D组、E组AST、ALT、TBIL明显降低(P<0.05),ALB和AFP、ALB、CK18 mRNA及HGF、EGF蛋白表达明显升高(P<0.05)。与E组比较,C组、D组AST、ALT、TBIL明显升高(P<0.05),ALB和AFP、ALB、CK18 mRNA及HGF、EGF蛋白表达明显降低(P<0.05)。免疫荧光结果显示,E组肝脏内携带绿色荧光蛋白数量明显高于A组、D组。结论 壮肝逐瘀煎联合BMMSC治疗可抗肝纤维化,可有效促进BMMSC向肝脏归巢,修复受损的肝组织。 展开更多
关键词 壮肝逐瘀煎 骨髓间充质干细胞移植 联合治疗 归巢 ccl4 肝纤维化
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虎杖苷对CCl_4损伤原代培养大鼠肝细胞的保护作用 被引量:47
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作者 黄兆胜 王宗伟 +2 位作者 刘明平 黎俏梅 吴庆光 《中国药理学通报》 CAS CSCD 北大核心 1998年第6期543-545,共3页
目的研究虎杖苷(PD)对CCl4损伤原代培养大鼠肝细胞的保护作用。方法原位灌流法分离大鼠肝细胞,培养24h后加入PD,同时造成CCl4损伤,分别于损伤后6,12,24和48h测培养液中谷丙转氨酶(ALT)、丙二醛(M... 目的研究虎杖苷(PD)对CCl4损伤原代培养大鼠肝细胞的保护作用。方法原位灌流法分离大鼠肝细胞,培养24h后加入PD,同时造成CCl4损伤,分别于损伤后6,12,24和48h测培养液中谷丙转氨酶(ALT)、丙二醛(MDA)和还原型谷胱甘肽(GSH)活性,48h后用MTT比色法测肝细胞存活率。结果PD1×10-7~1×10-4mol·L-1能不同程度地抑制ALT和MDA的上升,提高GSH水平,显著提高细胞存活率,以1×10-5mol·L-1效果最好。 展开更多
关键词 虎杖苷 大鼠 肝细胞 ccl4损伤 保护作用
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复方鳖甲软肝片对大鼠CCl_4肝纤维化模型疗效研究 被引量:35
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作者 杨艳宏 陈祥明 朱善济 《中国感染控制杂志》 CAS 2003年第4期249-251,245,共4页
目的 研究复方鳖甲软肝片对四氯化碳 (CCl4)诱导的大鼠肝纤维化模型的治疗效果。方法  80只SD大鼠 ,雌雄各半 ,CCl4和橄榄油 1 :4混合后 ,给大鼠腹部皮下注射 ,每周 2次 ,每次注射剂量为 0 .1 5mL/ 1 0 0 g ,制备肝纤维化模型。制模 ... 目的 研究复方鳖甲软肝片对四氯化碳 (CCl4)诱导的大鼠肝纤维化模型的治疗效果。方法  80只SD大鼠 ,雌雄各半 ,CCl4和橄榄油 1 :4混合后 ,给大鼠腹部皮下注射 ,每周 2次 ,每次注射剂量为 0 .1 5mL/ 1 0 0 g ,制备肝纤维化模型。制模 6周起开始用复方鳖甲软肝片灌胃治疗 ,每天 1次 ,连续治疗 3个月。于治疗前、治疗结束、停药后 1个月和 2个月每组各处死 8只大鼠 ,切取肝脏作病理切片检测。结果 复方鳖甲软肝片起效较慢 ,与模型组相比 ,在治疗刚结束时肝纤维化程度略有升高 (5 .2± 4 .3vs 4 .7± 0 .5 ,P >0 .0 5 ) ,停药 1个月后肝纤维化程度逐渐减轻 (2 .4± 3.1vs 6 .3± 3.1 ,P <0 .0 5 ) ,作用持续至停药后 2个月。复方鳖甲软肝片对肝纤维化大鼠肝脏的抗炎作用不十分明显 ,但具有较为明显的抗脂肪变作用 ,这种作用起效较慢 ,停药后 1个月才显现出来。 展开更多
关键词 复方鳖甲软肝片 大鼠 ccl4 肝纤维化 动物模型 灌胃
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小柴胡汤和柴胡—黄芩含药血清对CCl_4损伤肝细胞的影响 被引量:9
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作者 孙明瑜 谢鸣 +1 位作者 伊丽萦 张娜 《中国药理学通报》 CAS CSCD 北大核心 2004年第6期698-703,共6页
目的 建立CCl4肝细胞损伤模型 ,考察小柴胡汤及柴胡—黄芩配方含药血清对CCl4损伤肝细胞的保护作用。方法 制备小柴胡汤及柴胡—黄芩配方的大鼠含药血清 ,体外10mol·L-1CCl4诱导肝细胞损伤模型 ,观察体积分数为 0 1的含药血清... 目的 建立CCl4肝细胞损伤模型 ,考察小柴胡汤及柴胡—黄芩配方含药血清对CCl4损伤肝细胞的保护作用。方法 制备小柴胡汤及柴胡—黄芩配方的大鼠含药血清 ,体外10mol·L-1CCl4诱导肝细胞损伤模型 ,观察体积分数为 0 1的含药血清对损伤肝细胞增殖率、GPT、细胞形态学以及凋亡率的影响。结果 与正常组比较 ,模型组肝细胞增殖率降低 (P <0 0 1) ,细胞培养上清液中GPT含量升高 (P <0 0 1) ;与模型组比较 ,小柴胡汤及柴胡—黄芩配方组的肝细胞增殖率提高 (P <0 0 1) ,细胞培养上清液中GPT含量降低 (P <0 0 1)。倒置显微镜和Giemsa染色观察到模型组肝细胞存在着明显的坏死和凋亡 ,小柴胡汤及柴胡—黄芩配方的凋亡细胞明显减少。与正常组比较 ,CCL4模型组细胞凋亡增高 (P <0 0 1) ;与模型组比较 ,柴芩组和小柴胡汤全方组的细胞凋亡率降低 (P <0 0 1)。结论 小柴胡汤及柴胡—黄芩配方含药血清对体外CCl4诱导的肝细胞损伤有保护作用。CCl4引起的肝损伤同时存在着明显的凋亡和坏死 ,小柴胡汤及柴胡 -黄芩配方可能具有抗CCl4诱导的肝细胞凋亡的作用。 展开更多
关键词 小柴胡汤 柴胡-黄芩 ccl4 肝细胞损伤 凋亡 体外
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五味子对CCl_4中毒大鼠肝细胞核基质蛋白和结构的保护作用 被引量:27
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作者 陈玮莹 温博贵 +4 位作者 郑瑞明 吴贤英 陈爱芸 吴健谊 张艳美 《免疫学杂志》 CAS CSCD 北大核心 2006年第4期455-459,共5页
目的探讨五味子对中毒大鼠肝细胞核基质蛋白和结构的保护作用。方法将Wistar大鼠随机分为对照组、中毒组和治疗组。中毒组和治疗组大鼠经腹腔一次性注射200mLLCCl4(0.2mL100g体质量)致毒。治疗组以五味子提取液[0.5mL(100g·d)]灌胃... 目的探讨五味子对中毒大鼠肝细胞核基质蛋白和结构的保护作用。方法将Wistar大鼠随机分为对照组、中毒组和治疗组。中毒组和治疗组大鼠经腹腔一次性注射200mLLCCl4(0.2mL100g体质量)致毒。治疗组以五味子提取液[0.5mL(100g·d)]灌胃,中毒组以同量生理盐水灌胃,不同时间处死大鼠,光镜、电镜下观察肝脏细胞结构,并用免疫组化方法检测LaminB蛋白的表达和电泳分析核基质蛋白成分。结果光镜和电镜下,五味子提取物治疗后大鼠肝细胞病理改变明显减轻。五味子提取物促进了中毒大鼠肝细胞LaminB蛋白的表达、并有调节大鼠肝细胞核基质蛋白代谢的作用。结论五味子可能通过促进CCl4中毒大鼠肝细胞LaminB蛋白的表达和影响核基质蛋白的代谢而促进损伤肝细胞修复,对于CCl4中毒大鼠肝细胞核基质蛋白和结构具有保护作用。 展开更多
关键词 ccl4 大鼠 五味子 肝脏 核基质 LAMIN B
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壳寡糖及其衍生物对CCl_4诱导的小鼠肝损伤的保护作用 被引量:15
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作者 金黎明 杨艳 +3 位作者 刘万顺 韩宝芹 田文杰 范圣第 《山东大学学报(理学版)》 CAS CSCD 北大核心 2007年第7期1-4,12,共5页
研究壳寡糖(COS)、氨基葡萄糖(GlcNH2)和N-乙酰氨基葡萄糖(GlcNAc)对CCl4诱导的雄性昆明种小鼠肝毒性的保护作用,并探讨其可能机制.小鼠腹腔注射CCl4(20 mg/kg体重)24 h后,血清天门冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)活性明显提高,... 研究壳寡糖(COS)、氨基葡萄糖(GlcNH2)和N-乙酰氨基葡萄糖(GlcNAc)对CCl4诱导的雄性昆明种小鼠肝毒性的保护作用,并探讨其可能机制.小鼠腹腔注射CCl4(20 mg/kg体重)24 h后,血清天门冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)活性明显提高,引起肝脏脂质过氧化反应,巯基含量降低,总抗氧化能力(T-AOC)减弱,诱发基因毒性.提前连续12天分别灌胃给予COS,GlcNH2和GlcNAc(1.5 g/kg体重)能够显著诱导金属硫蛋白(MT)的表达,体内的抗氧化防御系统随之增强以抵抗CCl4诱导的氧化损伤.血清AST和ALT活性明显降低,肝脏丙二醛(MDA)生成被抑制,巯基含量,T-AOC明显恢复.但是,从DNA电泳结果反应出的基因毒性并未减轻.实验结果证明,提前给予COS,GlcNH2和GlcNAc对CCl4诱导的小鼠肝损伤能够起到有效的保护作用,其中,GlcNH2的作用效果最显著. 展开更多
关键词 ccl4 壳寡糖 抗氧化 肝保护
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