罗格列酮通过调节PPAR-γ/NFAT/IL-2信号通路治疗克罗恩病大鼠
| 作者: |
1姚嘉茵,
1刘涛,
2丛龙玲,
3鲁义,
1郅敏,
1高翔
1 中山大学附属第六医院消化内科，广州 510655 2 广州市中医医院消化内科，广州 510130 3 广州市中医医院麻醉科，广州 510130 |
| 通讯: |
高翔
Email: doctorgaoxiang@yeah.net |
| DOI: | 10.3978/j.issn.2095-6959.2019.08.002 |
| 基金: | 广东省中医药局科研项目(20191247)。 |
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[20 mg/(kg·d)灌胃]及GW9662组[1 mg/(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；RT-PCR方法检测结肠组织PPAR-γ/活化T细胞核因子(nuclear factor of activated 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。
关键词：
克罗恩病；罗格列酮；GW9662；过氧化物酶体增殖物激活受体γ
Rosiglitazone ameliorates Crohn’s disease rat models by regulating PPAR-γ/NFAT/IL-2 signaling pathway
CorrespondingAuthor: GAO Xiang Email: doctorgaoxiang@yeah.net
DOI: 10.3978/j.issn.2095-6959.2019.08.002
Foundation: This work was supported by the Scientific Research Project of Traditional Chinese Medicine Bureau of Guangdong Province, China (20191247).
Abstract
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.
Keywords：
Crohn’s disease; rosiglitazone; GW9662; peroxisome proliferator-activated receptor-γ