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Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease 被引量:1
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作者 Li-Fen Liu Yu-Tong Liu +5 位作者 Dan-Dan Wu Jie Cheng Na-Na Li Ya-Ni Zheng Liang Huang Qiong-Lan Yuan 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第9期2019-2028,共10页
Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In... Extracellular amyloid beta(Aβ) plaques are main pathological feature of Alzheimer’s disease.However,the specific type of neuro ns that produce Aβ peptides in the initial stage of Alzheimer’s disease are unknown.In this study,we found that 5-hydroxytryptamin receptor 3A subunit(HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice(an Alzheimer’s disease model) and patients with Alzheimer’s disease.To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques,we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model.Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons.These results suggest that HTR3A-positive interneurons may partially contribute to the generation of Aβ peptides.We treated 5.0-5.5-month-old model mice with tro pisetron,a HTR3 antagonist,for 8 consecutive weeks.We found that the cognitive deficit of mice was partially reversed,Aβ plaques and neuroinflammation we re remarkably reduced,the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice.These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer’s disease and inhibiting HTR3 partly reve rses the pathological changes of Alzheimer’s disease. 展开更多
关键词 5-hydroxytryptamin receptor 3 Alzheimer’s disease amyloid beta plaques CALCINEURIN cognitive deficits HTR3 interneurons iCa2+ nuclear factor of activated T-cells transgenic amyloid precursor protein and presenilin-1 mice TROPISETRON
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Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients:A matter of disease activity? 被引量:1
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作者 Antonietta Gerarda Gravina Iacopo Panarese +7 位作者 Maria Consiglia Trotta Michele D'Amico Raffaele Pellegrino Franca Ferraraccio Marilena Galdiero Roberto Alfano Paolo Grieco Alessandro Federico 《World Journal of Gastroenterology》 SCIE CAS 2024年第9期1132-1142,共11页
BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to asce... BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin family.However,data regarding their role in inflammatory bowel diseases(IBD)are currently unavailable.AIM This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic activity.METHODS Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and MC5R.Colonic sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal mucosa.CONCLUSION MC3R and MC5R are expressed in the colon of IBD patients.Furthermore,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology. 展开更多
关键词 Melanocortin 3 receptor Melanocortin 5 receptor Ulcerative colitis Crohn's disease Inflammatory bowel disease
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橘皮竹茹汤对化疗性异食癖大鼠模型5-羟色胺3受体蛋白和mRNA表达的影响 被引量:1
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作者 米金霞 艾纯颖 +3 位作者 李敏 吴中华 张超超 谢燕 《上海中医药杂志》 CSCD 2024年第4期19-25,共7页
目的观察橘皮竹茹汤对化疗性异食癖大鼠模型止呕作用及对5-羟色胺3受体(5-HT3R)蛋白和mRNA的影响。方法将36只Wistar雄性大鼠随机分为正常对照组、中药对照组(橘皮竹茹汤10.6 g/kg,不造模)、模型组、昂丹司琼组(2.6 mg/kg)、橘皮竹茹汤... 目的观察橘皮竹茹汤对化疗性异食癖大鼠模型止呕作用及对5-羟色胺3受体(5-HT3R)蛋白和mRNA的影响。方法将36只Wistar雄性大鼠随机分为正常对照组、中药对照组(橘皮竹茹汤10.6 g/kg,不造模)、模型组、昂丹司琼组(2.6 mg/kg)、橘皮竹茹汤低剂量组(5.3 g/kg)和橘皮竹茹汤高剂量组(10.6 g/kg),每组6只。各组大鼠给予相应干预措施6 d(每日2次)后,采用腹腔注射顺铂(6 mg/kg)的方式诱导建立化疗性异食癖大鼠模型,观察并记录造模后24 h内大鼠体质量、摄食量和高岭土摄入量的变化。继续干预1 d后,苏木精-伊红(HE)染色观察各组大鼠胃窦、回肠组织形态学变化;实时荧光定量逆转录聚合酶链式反应(RT-qPCR)法检测延髓、回肠组织中5-HT3R、色氨酸羟化酶(TPH)、单胺氧化酶A(MAOA)mRNA表达;Western blot法检测延髓组织中5-HT3R蛋白的表达。结果①与正常对照组比较,模型组大鼠体质量、摄食量降低(P<0.05),高岭土摄入量显著增加(P<0.05);与模型组比较,昂丹司琼组和橘皮竹茹汤低、高剂量组大鼠高岭土摄入量显著降低(P<0.05)。②HE染色显示,与正常对照组比较,模型组胃窦组织上皮细胞受损,固有层腺体排列疏松、紊乱,回肠上皮部分缺失,腺体排列紊乱;与模型组比较,昂丹司琼组和橘皮竹茹汤低、高剂组胃窦和回肠组织病理改变减轻。③RT-qPCR结果显示,与正常对照组比较,模型组大鼠延髓、回肠5-HT3R mRNA表达水平显著升高(P<0.05),回肠MAOA mRNA表达水平显著降低(P<0.05);与模型组比较,橘皮竹茹汤高剂量组大鼠延髓5-HT3R mRNA表达水平明显降低(P<0.05),橘皮竹茹汤低剂量组回肠TPH1 mRNA、橘皮竹茹汤高剂量组延髓TPH2 mRNA表达水平明显降低(P<0.05),昂丹司琼组、橘皮竹茹汤低剂量组、橘皮竹茹汤高剂量组回肠MAOA mRNA表达水平明显升高(P<0.05)。④Western blot结果显示,与正常对照组比较,模型组大鼠延髓5⁃HT3R蛋白表达水平显著升高(P<0.05);与模型组比较,橘皮竹茹汤高剂量组大鼠延髓5-HT3R蛋白表达水平显著降低(P<0.05)。结论橘皮竹茹汤可以通过抑制延髓5-HT3R蛋白和mRNA的表达,调控5-羟色胺合成与代谢相关酶,进而改善化疗导致的恶心呕吐。 展开更多
关键词 异食癖 肿瘤 化学疗法 恶心呕吐 橘皮竹茹汤 5-羟色胺3受体 经典名方 中药研究
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ICU急性呼吸衰竭患者外周血HCAR、DcR3、AQP-5水平与机械通气撤机结局的关系及价值分析
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作者 程亚娟 乔莉 《中国急救复苏与灾害医学杂志》 2024年第1期51-55,共5页
目的 探究重症监护室(ICU)急性呼吸衰竭患者外周血超敏C反应蛋白与白蛋白比值(HCAR)、诱骗受体3(DcR3)、水通道蛋白-5(AQP-5)水平与机械通气撤机结局的关系及临床价值。方法 选取连云港市第二人民医院2018年8月—2021年8月ICU急性呼吸... 目的 探究重症监护室(ICU)急性呼吸衰竭患者外周血超敏C反应蛋白与白蛋白比值(HCAR)、诱骗受体3(DcR3)、水通道蛋白-5(AQP-5)水平与机械通气撤机结局的关系及临床价值。方法 选取连云港市第二人民医院2018年8月—2021年8月ICU急性呼吸衰竭患者120例,均行机械通气治疗,在符合自主呼吸试验(SBT)指征且通过30 min SBT后撤机,根据撤机后48 h内是否再插管分为撤机成功组(87例)和撤机失败组(33例),撤机前采集外周血检测HCAR、DcR3、AQP-5水平,分析外周血HCAR、DcR3、AQP-5水平与撤机结局的关系及预测价值。结果 两组呼吸衰竭类型、合并器官功能障碍综合征(MODS)、肺部超声评分(LUS)、急性生理与慢性健康评价系统Ⅱ(APACHEⅡ)评分差异有统计学意义(P<0.05);撤机失败组外周血HCAR、DcR3高于撤机成功组,AQP-5低于撤机成功组(P<0.05);Pearson相关性分析显示外周血HCAR、DcR3与LUS、APACHEⅡ评分呈正相关,AQP-5与LUS、APACHEⅡ评分呈负相关(P<0.05);单因素、多因素分析均显示,外周血HCAR、DcR3、AQP-5影响撤机结局(P<0.05);外周血HCAR、DcR3、AQP-5预测撤机失败的截断值分别为4.10 mg/g、14.55μg/L、7.91μg/L,联合预测撤机失败的曲线下面积(AUC)为0.915(95%CI:0.850~0.958),大于各指标单独预测;以截断值为界分为低水平与高水平,外周血HCAR、DcR3高水平患者30 d生存率低于低水平患者,外周血AQP-5高水平患者30 d生存率高于低水平患者(P<0.05)。结论 ICU急性呼吸衰竭患者外周血HCAR、DcR3、AQP-5水平与撤机结局密切相关,联合检测可作为预测撤机失败的重要辅助手段,还能帮助临床判断死亡风险,为临床提供可靠的数据支持。 展开更多
关键词 重症监护室 急性呼吸衰竭 机械通气 超敏C反应蛋白与白蛋白比值 诱骗受体3 水通道蛋白-5 撤机结局
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血清TGR5 mRNA和BNIP3 mRNA在急性心肌梗死患者中的表达水平及临床意义
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作者 金长明 王青 《国际检验医学杂志》 CAS 2024年第9期1131-1135,1140,共6页
目的 探究血清G蛋白偶联胆汁酸受体5(TGR5)mRNA与Bcl-2/腺病毒QE1B-19kDa相互作用蛋白3(BNIP3)mRNA在急性心肌梗死(AMI)患者中的表达水平情况,以及二者对于术后心脏不良事件(MACE)发生的预测价值。方法 选取首都医科大学门头沟教学医院2... 目的 探究血清G蛋白偶联胆汁酸受体5(TGR5)mRNA与Bcl-2/腺病毒QE1B-19kDa相互作用蛋白3(BNIP3)mRNA在急性心肌梗死(AMI)患者中的表达水平情况,以及二者对于术后心脏不良事件(MACE)发生的预测价值。方法 选取首都医科大学门头沟教学医院2018年1月至2020年1月收治的98例进行经皮冠状动脉介入术(PCI)的AMI患者[AMI患者包括急性非ST段抬高型心肌梗死(NSTEMI)46例与急性ST段抬高型心肌梗死(STEMI)52例]为研究组,另选取同期90例体检健康者作为对照组。采用实时荧光定量PCR(qRT-PCR)检测血清TGR5 mRNA和BNIP3 mRNA表达水平,根据PCI术后随访结果将研究组分为MACE组(46例)和非MACE组(52例)。收集两组患者临床资料,采用Pearson法分析术后MACE组血清TGR5 mRNA与BNIP3 mRNA表达水平的相关性,采用受试者工作特征(ROC)曲线分析血清TGR5 mRNA和BNIP3 mRNA对于术后AMI患者MACE发生的预测价值,采用Logistic回归分析AMI患者术后MACE发生的影响因素。结果 研究组血清TGR5 mRNA表达水平显著低于对照组,血清BNIP3 mRNA表达水平显著高于对照组,差异有统计学意义(P<0.05);术后MACE组左心室射血分数(LVEF)、TGR5 mRNA表达水平显著低于非MACE组,血清肌酐(SCr)、红细胞分布宽度(RDW)、Killip分级Ⅲ+Ⅳ级比例、BNIP3 mRNA表达水平显著高于非MACE组,差异有统计学意(P<0.05);经Pearson相关性分析,血清TGR5 mRNA与BNIP3 mRNA表达水平呈负相关(r=-0.543,P<0.05);ROC曲线分析显示,血清TGR5 mRNA预测AMI患者MACE发生的曲线下面积(AUC)为0.704(95%CI:0.601~0.808),血清BNIP3 mRNA预测AMI患者MACE发生的AUC为0.762(95%CI:0.696~0.883),血清TGR5 mRNA与BNIP3 mRNA联合预测AMI患者术后MACE发生的AUC为0.867(95%CI:0.783~0.932),优于二者单独预测(Z_(二者联合-TGR5)=2.346,Z二者联合-BNIP3=1.715,P=0.019、0.043);Logistic回归分析结果显示,TGR5 mRNA、BNIP3 mRNA、RDW是AMI患者术后MACE发生的影响因素(P<0.05)。结论 TGR5 mRNA在AMI患者血清中呈低表达水平,BNIP3 mRNA在AMI患者血清中呈高表达表达,二者对于预测术后MACE发生具有重要意义。 展开更多
关键词 急性心肌梗死 G蛋白偶联胆汁酸受体5 Bcl-2/腺病毒E1B-19kDa相互作用蛋白3 术后心脏不良事件 预测价值
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Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions 被引量:1
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作者 Yinan DU Zhiwei LI +3 位作者 Yukui ZHAO Jing HAN Weiping HU Zhiqiang LIU 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2024年第1期23-37,共15页
5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT_(3)R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+and activation of subsequent voltage-gated ca... 5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT_(3)R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT_(3)R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT_(3)Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT_(3)Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and theγ-aminobutyric acid(GABA)“disinhibition”mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT_(3)R-induced GABA“disinhibition”mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT_(2)R-mediated regulation of anxiety reactions are also activated by 5-HT_(3)R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT_(3)Rs.However,given the circuit specific modulation of 5-HT_(3)Rs on emotion,systemic use of 5-HT_(3)R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT_(3)R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future. 展开更多
关键词 5-hydroxytryptamine type 3 receptor(5-HT_(3)R) ANXIETY Medial prefrontal cortex AMYGDALA HIPPOCAMPUS Periaqueductal gray
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Effects of 5-hydroxytryptamine Receptor on the Reaction of the Lower Esophageal Sphincter Under the Electrical Field Stimulation
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作者 Wei Li Hefei Li +5 位作者 Zhenqing Sun Ben Li Qiang Guo Tao Jiang Xinbo Liu Yong Feng 《Journal of Clinical and Nursing Research》 2020年第2期1-8,共8页
In the first and second parts of this study,5-hydroxytryptamine(5HT)receptors,including 5-HT3 and 5-HT4 with the highest expression level,were found in clasp and sling fibres of the lower esophageal sphincter(LES).Spe... In the first and second parts of this study,5-hydroxytryptamine(5HT)receptors,including 5-HT3 and 5-HT4 with the highest expression level,were found in clasp and sling fibres of the lower esophageal sphincter(LES).Specific 5-HT3 and 5-HT4 receptor agonists can induce the contraction effect of clasp and sling fibres of the LES while specific 5-HT7 receptor agonists showed no effects.In the study of this part,the in-vitro muscle tension measurement technology and EFS methods were used to detect the effect of the selective 5-HT receptor antagonist on the clasp and sling fibres of the in-vitro LES under the electrical field stimulation(EFS),and further to ensure the effect of 5-HT receptor in the LES neuroregulatory pathway,and deeply explore the effect of 5-HT receptor in the systolic and diastolic function regulation of the LES. 展开更多
关键词 5-hydroxytryptamine(5HT)receptors LOWER ESOPHAGEAL Sphincter(LES) In-vitro MUSCLE tension
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化疗患者5-羟色胺3受体拮抗剂路径化管理模式的建立与应用 被引量:1
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作者 高璐 李静 +4 位作者 周晓 黄元 虞琳 宋慧珠 杨钰华 《中国药房》 CAS 北大核心 2023年第4期493-496,共4页
目的建立化疗患者5-羟色胺3受体拮抗剂(5-HT3RA)路径化管理模式,提高化疗患者用药合理性。方法制定5-HT3RA规范化用药管控规则,并借助医疗智能及决策支持(MINDS)系统,以信息抓取结合医嘱前置审核的形式对使用5-HT3RA的化疗患者开展路径... 目的建立化疗患者5-羟色胺3受体拮抗剂(5-HT3RA)路径化管理模式,提高化疗患者用药合理性。方法制定5-HT3RA规范化用药管控规则,并借助医疗智能及决策支持(MINDS)系统,以信息抓取结合医嘱前置审核的形式对使用5-HT3RA的化疗患者开展路径化管理,对用药指征、用法用量、疗程等实施全程化干预。通过比较实施路径化管理前后5-HT3RA无指征用药、用法用量不合理、重复用药、疗程不合理的变化情况以及5-HT3RA人均药费变化情况,对干预效果进行分析。结果共纳入9181例患者,实施路径化管理后,无指征用药率降低0.48%,单次剂量、给药频次、重复用药、疗程(化疗结束后3 d仍使用5-HT3RA)的不合理率分别降低10.48%、0.65%、1.33%、0.34%,5-HT3RA人均药费降低13.72元,以上差异均有统计学意义(P<0.05)。结论我院建立的化疗患者5-HT3RA路径化管理模式有效提高了用药合理性,为临床合理用药提供了新思路。 展开更多
关键词 5-羟色胺3受体拮抗剂 化疗患者 路径化管理 信息化
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电针对功能性消化不良模型大鼠行为学及下丘脑5-HT3R、CRH mRNA表达的影响 被引量:2
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作者 姚函伶 乐薇 +4 位作者 范建超 刘浩 徐派的 吴贻森 杨格格 《陕西中医》 CAS 2023年第6期699-703,共5页
目的:观察电针“印堂”“内关”“足三里”对功能性消化不良(FD)大鼠的行为模式及下丘脑5-羟色胺3受体(5-HT3R)、促肾上腺皮质激素释放激素(CRH)mRNA表达水平的影响。方法:模型组和电针组大鼠采用多因素造模法复制FD模型。电针组电针“... 目的:观察电针“印堂”“内关”“足三里”对功能性消化不良(FD)大鼠的行为模式及下丘脑5-羟色胺3受体(5-HT3R)、促肾上腺皮质激素释放激素(CRH)mRNA表达水平的影响。方法:模型组和电针组大鼠采用多因素造模法复制FD模型。电针组电针“印堂”“内关”“足三里”,每次干预30 min, 1次/d,连续2周。观察各组大鼠治疗前后的体重变化;旷场实验检测电针对FD模型大鼠新环境的自主适应能力以及紧张度的影响;HE染色法观察大鼠胃窦形态的改变;实时荧光定量PCR法测定大鼠下丘脑5-HT3R、CRH mRNA的表达。结果:干预前,模型组和电针组大鼠体重、旷场自主运动距离以及运动速度均低于空白组(P<0.01)。干预后,电针组大鼠体重、旷场自主运动距离以及运动速度较干预前升高,均高于模型组(P<0.01)。模型组大鼠胃窦组织黏膜下层轻度水肿,黏膜层排列疏松,伴有少量的淋巴细胞存在;空白组和电针组大鼠胃窦组织结构完整,黏膜层排列整齐,胃腺间质无异常增生,不存在明显病理改变。与空白组相比,模型组大鼠下丘脑5-HT3R、CRH mRNA表达明显上升(均P<0.05)。与模型组相比,电针组大鼠下丘脑5-HT3R、CRH mRNA表达显著降低(均P<0.05)。结论:电针能改善FD大鼠消化不良症状,提高FD大鼠自主运动水平,减轻大鼠胃窦炎症细胞浸润,其机制可能与抑制下丘脑5-HT3R、CRH mRNA的表达有关。 展开更多
关键词 功能性消化不良 电针 大鼠 下丘脑 5-羟色胺3受体 促肾上腺皮质激素释放激素
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5-羟色胺受体3拮抗剂通过IκBα/NF-κB信号通路抑制脂多糖诱导RAW264.7细胞炎症反应 被引量:1
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作者 邓邺云 任晓曦 +2 位作者 刘康瑞 陈茜 张建亮 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2023年第5期750-758,共9页
在败血症等炎症相关疾病中,巨噬细胞过度产生的炎症因子在疾病的发病机制中发挥关键作用。5-羟色胺受体3(5-hydroxytryptamine receptor 3,5-HT_(3)R)拮抗剂,近来被发现在免疫系统中具有抑制炎症的作用,但其具体机制尚不清楚。本文使用... 在败血症等炎症相关疾病中,巨噬细胞过度产生的炎症因子在疾病的发病机制中发挥关键作用。5-羟色胺受体3(5-hydroxytryptamine receptor 3,5-HT_(3)R)拮抗剂,近来被发现在免疫系统中具有抑制炎症的作用,但其具体机制尚不清楚。本文使用脂多糖(lipopolysaccharides,LPS)刺激小鼠巨噬细胞系RAW 264.7细胞,引发巨噬细胞炎症相关蛋白质的表达和炎症因子的释放。结果显示,在RAW 264.7细胞中,与无处理组相比,LPS以剂量和时间依赖的方式促进炎症相关蛋白质的表达和炎症因子的释放。进一步使用5-HT_(3)R拮抗剂格拉司琼(granisetron,GA)进行预处理,检测其抗炎作用。蛋白质免疫印迹和酶联免疫吸附测定的结果表明,与LPS处理组相比,随着GA浓度的升高,其抑制LPS诱导的RAW 264.7细胞炎症的效果越好(P<0.05)。同时,细胞活力和细胞毒性的结果也表明,所使用的GA对细胞不造成损伤。另外,通过免疫荧光实验和双荧光素酶检测表明,GA可以抑制LPS诱导的NF-κB的核移位和转录活性;进一步的蛋白质免疫印迹结果表明,GA可以通过抑制IκBα的磷酸化而抑制其降解,从而抑制NF-κB的功能。总之,本文的结果提示,GA可以通过抑制IκBα/NF-κB信号通路,抑制RAW 264.7巨噬细胞中炎症相关蛋白质的表达和炎症因子的释放。本研究结果为进一步探究5-HT_(3)R拮抗剂抗炎的分子机制,以及研发治疗败血症等炎症相关疾病的药物提供科学依据。 展开更多
关键词 败血症 抗炎 5-羟色胺受体3 格拉司琼 IκBα/NF-κB信号通路
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5-HT_(3)受体抑制剂预防成人术后恶心呕吐的研究进展 被引量:2
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作者 王珮屹 姜远旭 《中国医药指南》 2023年第4期64-66,共3页
术后恶心呕吐(PONV)是常见的术后并发症之一。PONV增加了患者痛苦、医疗费用及术后风险。临床中多种因素可导致PONV的发生,如吸入性麻醉药、阿片类药物、腹腔镜所建立的气腹等,可通过5-HT_(3)受体等各种受体等介导恶心或呕吐的发生。因... 术后恶心呕吐(PONV)是常见的术后并发症之一。PONV增加了患者痛苦、医疗费用及术后风险。临床中多种因素可导致PONV的发生,如吸入性麻醉药、阿片类药物、腹腔镜所建立的气腹等,可通过5-HT_(3)受体等各种受体等介导恶心或呕吐的发生。因此阻滞5-HT_(3)受体神经传导通路是预防PNOV的重要方法。本文综述了5-HT_(3)受体抑制剂应用于预防成人PONV研究进展,为提高围手术期患者就医体验、缩短住院时间提供一定的参考。 展开更多
关键词 手术后恶心呕吐 帕洛诺司琼 5-HT_(3)受体
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益气养阴祛瘀方对干燥综合征NOD小鼠颌下腺AQP5、M3R表达的影响 被引量:3
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作者 任雅婷 刘丹 +1 位作者 周东海 王新昌 《中药新药与临床药理》 CAS CSCD 北大核心 2023年第5期613-619,共7页
目的研究益气养阴祛瘀方(黄芪、生地黄、玄参、丹参、益母草等)对干燥综合征NOD小鼠颌下腺水通道蛋白5(AQP5)以及毒蕈碱样胆碱能受体3(M3R)表达的影响。方法将30只NOD小鼠随机分为5组:模型组、西药组(硫酸羟氯喹60 mg·kg^(-1))及... 目的研究益气养阴祛瘀方(黄芪、生地黄、玄参、丹参、益母草等)对干燥综合征NOD小鼠颌下腺水通道蛋白5(AQP5)以及毒蕈碱样胆碱能受体3(M3R)表达的影响。方法将30只NOD小鼠随机分为5组:模型组、西药组(硫酸羟氯喹60 mg·kg^(-1))及益气养阴祛瘀方低、中、高剂量组(11.147、22.295、44.590 g·kg^(-1)),每组6只。每日灌胃给药1次,连续给药8周。给药后第0、4、8周连续测量小鼠每日饮水量;给药结束后,分离小鼠双侧颌下腺并称定其质量,计算小鼠颌下腺指数;采用HE染色法进行颌下腺组织病理学观察,计算灶性指数评分;RT-qPCR法检测小鼠颌下腺组织AQP5、M3R mRNA表达水平;Western Blot法检测小鼠颌下腺组织AQP5、M3R蛋白表达水平;免疫组化法检测颌下腺组织AQP5蛋白表达水平;ELISA法检测血清干扰素γ(IFN-γ)、白细胞介素10(IL-10)含量。结果给药前,与模型组比较,益气养阴祛瘀方低、中、高剂量组及西药组NOD小鼠的日饮水量无明显变化(P>0.05);给药第4、8周,与模型组比较,益气养阴祛瘀方低、中、高剂量组及西药组NOD小鼠的日饮水量均显著减少(P<0.01)。模型组小鼠颌下腺淋巴细胞浸润明显并形成较多浸润灶;与模型组比较,益气养阴祛瘀方低、中、高剂量组及西药组NOD小鼠的颌下腺淋巴细胞浸润情况得到明显改善,浸润灶数量明显减少,灶性指数评分显著降低(P<0.01),颌下腺组织AQP5、M3R蛋白表达水平明显升高(P<0.05,P<0.01),血清IL-10水平明显升高(P<0.05,P<0.01);益气养阴祛瘀方高剂量组和西药组NOD小鼠的颌下腺指数明显升高(P<0.05);益气养阴祛瘀方中、高剂量组和西药组NOD小鼠颌下腺组织AQP5、M3R mRNA表达明显上调(P<0.05,P<0.01),血清IFN-γ含量显著降低(P<0.01)。结论益气养阴祛瘀方对NOD小鼠唾液腺损伤具有改善作用,可能通过上调AQP5、M3R表达,抑制颌下腺淋巴细胞浸润,改善唾液分泌功能,从而减缓干燥综合征进程。 展开更多
关键词 益气养阴祛瘀方 干燥综合征 NOD小鼠 颌下腺 水通道蛋白5 毒蕈碱样胆碱能受体3
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Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs 被引量:9
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作者 Hiroki Morita Erito Mochiki +11 位作者 Nobuyuki Takahashi Kiyoshi Kawamura Akira Watanabe Toshinaga Sutou Atsushi Ogawa Mitsuhiro Yanai Kyoichi Ogata Takaaki Fujii Tetsuro Ohno Souichi Tsutsumi Takayuki Asao Hiroyuki Kuwano 《World Journal of Gastroenterology》 SCIE CAS 2013年第39期6604-6612,共9页
AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs ... AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious dogs.METHODS:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist administration.The force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and colon.Test materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive state.The effects of these receptor antagonists on normal gastrointestinal motor activity were analyzed.RESULTS:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal ileum.The 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor activity.In the proximal colon,the inhibitory effect was dose dependent.Dose dependency,however,was not observed in the distal colon.The 5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.CONCLUSION:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor activity.The5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity. 展开更多
关键词 5-hydroxytryptamine receptor antagonist COLONIC motility IRRITABLE bowel syndrome
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Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist inhibits apoptosis of retinal ganglion cells in a rabbit model of optic nerve injury 被引量:1
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作者 Ruijia Wang Xinping Luan Yiti Mu Hongyu Jia Jingxuan Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2012年第10期731-735,共5页
A rabbit model of traumatic optic nerve injury, established by occlusion of the optic nerve using a vascular clamp, was used to investigate the effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid recep... A rabbit model of traumatic optic nerve injury, established by occlusion of the optic nerve using a vascular clamp, was used to investigate the effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist GYKI 52466 on apoptosis of retinal ganglion cells following nerve injury. Hematoxylin-eosin staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that retinal ganglion cells gradually decreased with increasing time of optic nerve injury, while GYKI 52466 could inhibit this process. The results demonstrate that following acute optic nerve injury, apoptosis of retinal ganglion cells is a programmed process, which can be inhibited by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist. 展开更多
关键词 optic nerve injury retinal ganglion cells GLUTAMATE alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor
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Support vector classification for SAR of 5-HT3 receptor antagonists 被引量:1
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作者 杨善升 陆文聪 +1 位作者 纪晓波 陈念贻 《Journal of Shanghai University(English Edition)》 CAS 2006年第4期366-370,共5页
In this work, support vector classification (SVC) algorithm was used to build structure-activity relationship (SAR) model of the 5-hydroxytryptamine type 3 (5-HT3 ) receptor antagonists with 26 compounds. In a b... In this work, support vector classification (SVC) algorithm was used to build structure-activity relationship (SAR) model of the 5-hydroxytryptamine type 3 (5-HT3 ) receptor antagonists with 26 compounds. In a benchmark test, SVC was compared with several techniques of machine learning currently used in the field. The prediction performance of the model was discussed on the basis of the leave-one-out cross-validation. The results show that the accuracy of prediction of SVC model was higher than those of back propagation artificial neural network (BP ANN), K-nearest neighbor (KNN) and Fisher methods. 展开更多
关键词 support vector classification structure-activity relationship CHEMOMETRICS 5-HT3 receptor antagonists.
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小陷胸汤对5-氟尿嘧啶介导的小鼠肠黏膜损伤的保护作用研究
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作者 秦美洁 叶倩倩 +1 位作者 丁芮 黄金玲 《海南医学院学报》 CAS 北大核心 2024年第19期1441-1450,共10页
目的:探究小陷胸汤对5-氟尿嘧啶(5-fluorouracil,5-FU)介导的小鼠肠黏膜损伤的保护作用。方法:将100只SPF级雄性ICR小鼠随机分为正常对照组、模型组、小陷胸汤低、中、高剂量(8.3、16.6、33.2g/kg)组。除正常对照组外,其余各组采用5-FU(... 目的:探究小陷胸汤对5-氟尿嘧啶(5-fluorouracil,5-FU)介导的小鼠肠黏膜损伤的保护作用。方法:将100只SPF级雄性ICR小鼠随机分为正常对照组、模型组、小陷胸汤低、中、高剂量(8.3、16.6、33.2g/kg)组。除正常对照组外,其余各组采用5-FU(30 mg/kg,ip,7 d)诱导肠黏膜损伤小鼠模型。小陷胸汤给药组造模同时按照设定剂量以10 mL·kg^(-1)·d^(-1)灌胃,正常对照组和模型组给予等量蒸馏水,连续处理7 d。采用苏木素-伊红染色法(HE)观察小肠的病理形态学变化并测定肠绒毛高度/隐窝深度(VH:CD)比值;采用阿利新蓝染色法(AB)测定小肠黏膜杯状细胞数量;采用分光光度法检测血清内毒素(ET)、D-乳酸(D-LA)及小肠组织二胺氧化酶(DAO)水平;采用酶联免疫吸附法(ELISA)检测血清肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平;采用实时荧光定量聚合酶链式反应法(RT-qPCR)检测小肠组织IL-6、信号转导和转录激活因子3(STAT3)和表皮生长因子受体(EGFR)mRNA表达;采用Western blot法检测小肠组织IL-6、STAT3及EGFR蛋白表达。结果:与正常对照组相比,模型组小鼠体质量显著降低,腹泻评分、粪便质量、粪便含水量及小肠推进率明显升高(P<0.01),小肠黏膜VH:CD比值和杯状细胞数量降低(P<0.01),血清ET和D-LA水平升高,小肠组织DAO水平降低(P<0.05),脾指数和胸腺指数降低(P<0.01),血清IL-6、TNF-α水平升高(P<0.05),小肠组织IL-6、STAT3 mRNA表达升高,EGFR mRNA表达降低(P<0.01);小肠组织IL-6、STAT3蛋白表达升高,EGFR蛋白表达降低(P<0.01)。与模型组相比,小陷胸汤能够明显改善上述指标(P<0.05)。结论:小陷胸汤对5-FU介导的肠黏膜损伤具有保护作用,其作用机制可能与小陷胸汤激活EGFR信号转导,下调IL-6/STAT3信号通路,减轻5-FU诱导的肠黏膜炎症反应,改善免疫功能有关。 展开更多
关键词 小陷胸汤 5-氟尿嘧啶(5-FU) 肠黏膜损伤 表皮生长因子受体(EGFR) 白细胞介素6(IL-6)/信号转导和转录激活因子3(STAT3)信号通路
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Inhibition of 5-HT_3 Receptors-activated Currents by Cannabinoids in Rat Trigeminal Ganglion Neurons
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作者 石波 杨蓉 +6 位作者 王晓慧 刘海霞 邹丽 胡晓群 吴建萍 邹安若 刘玲华 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2012年第2期265-271,共7页
This study investigated the modulatory effect of synthetic cannabinoids WIN55,212-2 on 5-HT3 receptor-activated currents (I5-HT3) in cultured rat trigeminal ganglion (TG) neurons using whole-cell patch clamp technique... This study investigated the modulatory effect of synthetic cannabinoids WIN55,212-2 on 5-HT3 receptor-activated currents (I5-HT3) in cultured rat trigeminal ganglion (TG) neurons using whole-cell patch clamp technique. The results showed that: (1) The majority of examined neurons (78.70%) were sensitive to 5-HT (3–300 μmol/L). 5-HT induced inward currents in a concentration-dependent manner and the currents were blocked by ICS 205-930 (1 μmol/L), a selective antagonist of the 5-HT3 receptor; (2) Pre-application of WIN55,212-2 (0.01–1 μmol/L) significantly inhibited I5-HT3 reversibly in concentration-dependent and voltage-independent manners. The concentra-tion-response curve of 5-HT3 receptor was shifted downward by WIN55,212-2 without any change of the threshold value. The EC50 values of two curves were very close (17.5±4.5) mmol/L vs. (15.2±4.5) mmol/L and WIN55,212-2 decreased the maximal amplitude of I5-HT3 by (48.65±4.15)%; (3) Neither AM281, a selective CB1 receptor antagonist, nor AM630, a selective CB2 receptor antagonist reversed the inhibition of I5-HT3 by WIN55,212-2; (4) When WIN55,212-2 was given from 15 to 120 s before 5-HT application, inhibitory effect was gradually increased and the maximal inhibition took place at 90 s, and the inhibition remained at the same level after 90 s. We are led to concluded that-WIN55,212-2 inhibited I5-HT3 significantly and neither CB1 receptor antagonist nor CB2 receptor antagonist could reverse the inhibition of I5-HT3 by WIN55,212-2. Moreover, WIN55,212-2 is not an open channel blocker (OCB) of 5-HT3 receptor. WIN55,212-2 significantly inhibited 5-HT-activated currents in a non-competitive manner. The inhibition of I5-HT3 by WIN55,212-2 is probably new one of peripheral analgesic mechanisms of WIN55,212-2, but the mechanism by which WIN55,212-2 inhibits I5-HT3 warrants further investigation. 展开更多
关键词 WIN55 212-2 5-HT3 receptor CB1 receptor CB2 receptor trigeminal ganglion neuron whole-cell patch clamp
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Role of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor regulation in stress-induced pain chronification
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作者 Sufang Liu Feng Tao 《World Journal of Biological Chemistry》 CAS 2017年第1期1-3,共3页
Persistent postsurgical pain is a serious issue in public health, which has received increased interest in recent years. Previous studies have reported that psychological factors promote the development of chronic pos... Persistent postsurgical pain is a serious issue in public health, which has received increased interest in recent years. Previous studies have reported that psychological factors promote the development of chronic postsurgical pain. However, it is unclear how chronification of postsurgical pain occurs. The α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor(AMPA) phosphorylation in the central nervous system plays a critical role in synaptic plasticity and contributes to central sensitization and chronic pain development. Here, we discuss the role of AMPA receptor regulation in stress-induced pain chronification after surgery. 展开更多
关键词 α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor phosphorylation Stress Pain chronification
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脊髓5-HT_(1A)受体和5-HT_(3)受体参与的心血管反应 被引量:4
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作者 邱学才 王敬玲 +1 位作者 石玉顺 韩济生 《生理学报》 CAS CSCD 北大核心 1991年第6期548-555,共8页
给清醒大鼠脊髓蛛网膜下腔注射(ith)5-羟色胺(5-HT)1.56、3.125、6.25和12.5μg/1Oμl后引起明显血压升高,并呈量效关系,但心率(HR)无明显改变。Ith 5-HT 再摄取抑制剂 fluoxetine(10μg/10μ1)后也使平均动脉压(mABP)明显上升,这一效... 给清醒大鼠脊髓蛛网膜下腔注射(ith)5-羟色胺(5-HT)1.56、3.125、6.25和12.5μg/1Oμl后引起明显血压升高,并呈量效关系,但心率(HR)无明显改变。Ith 5-HT 再摄取抑制剂 fluoxetine(10μg/10μ1)后也使平均动脉压(mABP)明显上升,这一效应可被5-HT 受体阻断剂肉桂硫胺(cinanserin 25μg/1Oμl)完全阻断。8-OH-DPAT 和2-Methylhydroxy-tryptamine 分别为5-HT_(1A)受体和5-HT_3受体的激动剂,在 ith 8-OH-DPAT(2.5,5.0,1Oμg/1Oμl)后 mABP 明显上升,但 HR 减慢;相反,ith 2-Methylhydroxytryptamine 之后则使 mABP 明显降低,HR 无明显变化。以上结果表明,脊髓中5-HT 可通过激活5-HT_(1A)受体引起血压升高,激活5-HT_3受体则引起血压降低。这一发现对有关5-HT 中枢效应的不同报道提出了一种可能的解释。 展开更多
关键词 5-羟色胺 FLUOXETINE 5-HT_(1A)受体 5-HT_(3)受体 脊髓蛛网膜下腔注射 血压
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健脾化湿颗粒对D-IBS模型大鼠脑中5-HT及5-HTR3,5-HTR4表达的影响 被引量:7
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作者 王迎寒 赵素微 +6 位作者 陈光晖 刘玉玲 胡楠 杜海燕 靳继伟 于海龙 张晓峰 《世界华人消化杂志》 CAS 2016年第2期255-261,共7页
目的:从前额叶皮质、海马及下丘脑中5-羟色胺(5-hydroxytryptamine,5-HT)和5-羟色胺受体3(5-hydroxytryptamine receptor3,5-HTR3),5-羟色胺受体4(5-HTR4)角度探讨健脾化湿颗粒改善腹泻型肠易激综合征(diarrhea-predominant irritable b... 目的:从前额叶皮质、海马及下丘脑中5-羟色胺(5-hydroxytryptamine,5-HT)和5-羟色胺受体3(5-hydroxytryptamine receptor3,5-HTR3),5-羟色胺受体4(5-HTR4)角度探讨健脾化湿颗粒改善腹泻型肠易激综合征(diarrhea-predominant irritable bowel syndrome,D-IBS)模型大鼠结肠运动和内脏敏感性的作用机制.方法:采用番泻叶灌胃结合束缚应激法建立D-IBS大鼠模型,应用健脾化湿颗粒进行干预,采用酶联免疫法(ELISA)检测大鼠海马中5-HT含量,采用免疫组织化学法检测前额叶皮质、海马及下丘脑中5-HT、5-HTR3、5-HTR4阳性表达,采用逆转录-聚合酶链反应法检测海马中5-H T R3 m R N A和5-H T R4m RNA的表达水平.结果:与正常组相比,模型组海马中5-HT含量(327.30±22.35 vs 265.33±13.60),前额叶皮质、海马、下丘脑中5-HT阳性表达(0.16±0.02 vs 0.08±0.01,0.19±0.02 vs 0.09±0.01,0.17±0.02 vs 0.08±0.01)明显升高(P<0.01);前额叶皮质、海马、下丘脑中5-HTR3阳性表达(0.29±0.02 vs 0.10±0.01,0.23±0.02 vs 0.09±0.01,0.22±0.02 vs 0.09±0.02)及5-HTR4阳性表达(0.25±0.02 vs0.11±0.01,0.28±0.02 vs 0.10±0.02,0.27±0.02 vs 0.11±0.02)明显升高(P<0.01);海马中5-H T R3 m R N A和5-H T R4 m R N A的表达(0.54±0.01 vs 0.17±0.05,0.73±0.08 vs 0.10±0.02)显著升高(P<0.01).与模型组相比,阳性对照组、中、高剂量组海马中5-H T含量(298.92±12.16、286.29±24.43、279.86±20.05 vs 327.30±22.35)显著下降(P<0.05,P<0.01),中、高剂量组前额叶皮质中5-HT表达(0.12±0.01、0.11±0.01 vs 0.16±0.02)显著下降(P<0.01),阳性对照组、中、高剂量组海马、下丘脑中5-H T表达显著下降(P<0.05,P<0.01);各治疗组前额叶皮质、海马、下丘脑中5-H T R3表达及5-H T R4表达下降显著(P<0.05,P<0.01);各治疗组海马中5-H T R3 m R N A表达及5-H T R4 m R N A表达显著降低(P<0.05,P<0.01).结论:健脾化湿颗粒可能通过下调脑中5-HT、5-HTR3、5-HTR4表达来改善D-IBS模型大鼠结肠运动和内脏敏感性. 展开更多
关键词 腹泻型肠易激综合征 5-羟色胺 5-羟色胺3受体 5-羟色胺4受体 健脾化湿颗粒
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