摘要
目的:探讨罗格列酮对CD大鼠模型的作用及具体机制。方法:采用三硝基苯磺酸(trinitrobenzenesulfonic acid,TNBS)诱导建立实验性结肠炎大鼠模型,40只SD大鼠随机分为空白对照组、模型组、罗格列酮组[20mg/(kg·d)灌胃]及GW9662组[1mg/(kg·d)灌胃]。对大鼠CD疾病活动指数(disease activity index,DAI)、结肠大体损伤指数(colon macroscopic damage index,CMDI)和结肠组织学损伤指数(tissues damage index,TDI)进行评分;心脏穿刺取血检测超敏C反应蛋白(hypersensitive C-reactive protein,Hs-CRP)以及红细胞沉降率(sedimentation rate,ESR)变化;RTPCR方法检测结肠组织PPAR-γ/活化T细胞核因子(nuclear factor o factivated T-cells,NFAT)/白介素-2(interleukin-2,IL-2)上下游基因表达的变化。结果:罗格列酮干预有效降低DAI,CMDI及TDI评分(P<0.05),下调血清炎性指标,促进大鼠肠黏膜PPAR-γ基因的表达,抑制NFAT及下游IL-2基因表达。结论:罗格列酮有效减少实验性结肠炎大鼠的临床活动,改善大体及组织学改变,其治疗作用可能通过调节PPAR-γ/NFAT/IL-2信号通路实现。
Objective:To clarify the effect and mechanisms of rosiglitazone on CD rat model.Methods:Rat model of experimental colitis induced by trinitrobenzenesulfonic acid (TNBS) was established.Forty SD rats were randomly divided into a control group,a model group,a rosiglitazone group [20 mg/(kg·d), oral gavage] and GW9662 group [1 mg/(kg·d),oral gavage].The disease activity index (DAI),colon macroscopic damage index (CMDI) and tissues damage index (TDI) were evaluated.Levels of inflammation factors including sedimentation rate (ESR) and hypersensitive C-reactive protein (hs- CRP) were measured via cardiac puncture blood sampling.Gene expressions of PPAR-γ/nuclear factor of activated T-cells (NFAT)/interleukin-2 (IL-2) in colon tissue were detected by RT-PCR. Results:Rosiglitazone effectively decreased the scores of DAI,CMDI and TDI (P<0.05),down-regulated the inflammatory index of serum,promoted gene expression of PPAR-γ and inhibited gene expressions of NFAT and downstream IL-2 in colon tissue.Conclusion:Rosiglitazone effectively reduces the clinical activity and improves the gross and histological changes in experimental colitis rats,the therapeutic effect of is probably achieved by regulating the PPAR-γ/NFAT/IL-2 signaling pathway.
作者
姚嘉茵
刘涛
丛龙玲
鲁义
郅敏
高翔
YAO Jiayin;LIU Tao;CONG Longling;LU Yi;ZHI Min;GAO Xiang(Department of Gastroenterology,Sixth Affiliated Hospital of Sun Yat-Sen University,Guangzhou 510655;Department of Gastroenterology,Guangzhou Hospital of Traditional Chinese Medicine,Guangzhou 510130;Department of Anesthesiology,Guangzhou Hospital of Traditional Chinese Medicine,Guangzhou 510130,China)
出处
《临床与病理杂志》
2019年第8期1622-1627,共6页
Journal of Clinical and Pathological Research
基金
广东省中医药局科研项目(20191247)~~