摘要
目的探讨别旁茶苷Jasminoside(SC)对溃疡性结肠炎(UC)小鼠的治疗作用及其机制。方法将小鼠随机分为正常对照组,模型组,柳氮磺胺吡啶(SASP)组和SC高、中、低剂量组。除正常对照组外,其余各组采用2,4,6-三硝基苯磺酸(TNBS)建立小鼠结肠炎的模型,给药治疗7d后取材,显微镜下观察结肠黏膜损伤情况,采用酶联免疫吸附剂测定(ELISA)法测定结肠中α肿瘤坏死因子(TNF-α),白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和转化生长因子-β1(TGF-β1)水平;采用逆转录-聚合酶链反应(RT-PCR)法检测结肠组织中细胞色素P4503A4酶(CYP3A4)、孕烷X受体(PXR)、TNF-α、IL-6和IL-1β mRNA表达;采用Western Blot法检测结肠组织中CYP3A4和核转录因子P65(NF-κBP65)表达。结果与正常对照组相比,模型组有明显的病理变化,小鼠结肠黏膜和粘膜下层的多形核细胞浸润情况较严重,出现溃疡和上皮杯状细胞缺失的情况;与TNBS组相比,SASP组和SC各给药组结肠组织的TNF-α、IL-6、IL-1β和TGF-β1的水平及TNF-α、IL-6和IL-1β mRNA的表达水平均有显著下降,并呈剂量依赖性,SASP和SC组中CYP3A4和PXR的mRNA水平显着上调;与正常对照组相比,TNBS组NF-κBP65蛋白表达显着增加,而SASP组和SC组中NF-κBP65表达下降。结论SC对溃疡性小鼠结肠炎有显著疗效,其可能通过激活PXR、CYP3A,抑制NF-κB的表达,降低炎症因子TNF-α,IL-6、IL-1β和TGF-β1的水平来发挥保护作用。
Objective To investigate the therapeutic effect and mechanism of Jasminoside (SC) on Ulcerative colitis (UC) in mice.Methods The mice were randomly divided into normal group,model group,Sulfasalazine (SASP) group and SC high,middle and low dose groups.Except for normal group,mice in other groups were treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish IBD models.Colon mucosal lesions were observed after the mice were treated for 7 days.The levels of TNF-α,IL-6,IL-1β and TGF-β1 in colon were determined by enzyme-linked immunosorbent assay (ELISA).The expression of cytochrome P4503A4 (CYP3A4),progesterone X receptor(PXR),TNF-α,IL-6 and IL-1β mRNA were detected by RT-PCR,and the expression of CYP3A4 and nuclear transcription factor P65 (NF-κBP65) were detected by Western Blot.Results Compared with the model group,the histopathology of colons were improved in the SASP and SC groups.SASP-and SC-treated mice had lower levels of TNF-α,IL-6,IL-1β,TGF-β1 and NF-κBP65 in the colonic tissues,and higher levels of CYP3A4 and PXR mRNA expression than the model mice with dose dependence.Conclusion SC has beneficial effects on treating ulcerative colitis in mice mainly by activating PXR and CYP3A and inhibiting the expression of NF-κBP65,and decreasing the production of inflammatory factors TNF-α,IL-6,IL-1β and TGF-β1.
作者
张镖
宋雨鸿
周晓芸
王凤云
李卫东
韩亮
ZHANG Biao;SONG Yuhong;ZHOU Xiaoyun;WANG Fengyun;LI Weidong;HAN Liang(School of Pharmacy,Xinhua College of Sun Yat-sen University,Guangzhou 510520 Guangdong,China;Guangzhou First People's Hospital,Guangzhou 5101802 Guangdong,China;Guangdong Pharmaceutical University,Guangzhou510006 Guangdong,China;Guangdong Engineering Research Center for Light and Health,Guangzhou 510000 Guangdong,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2019年第5期547-552,共6页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家自然科学基金项目(81703816)
广州市科技计划项目(201707010278)
