Department of Gastroenterology, Medical University of Lublin, Lublin, Poland.
Med Sci Monit. 2011 Apr;17(4):BR116-24. doi: 10.12659/msm.881712.
This study sought to define the mechanism by which PPAR-γ ligands affect the course of experimentally induced colitis in rats.
MATERIAL/METHODS: Inflammation was induced in Wistar rats by a single rectal administration of 2,4,6,-trinitrobenzene sulfonic acid (TNBS). The antagonist of PPARγ antagonist, bisphenol A diglycidyl ether (BADGE), was administrated intraperitoneally 120 mg/kg 4 times every other day. Rosiglitazone 8 mg/kg was administrated by gastric tube 4 times. Body weight was measured daily. After killing, the large intestinal tissue was weighed and collected for histopathologic and immunoenzymatic tests. Levels of IL-6, IL-10, and myeloperoxidase (MPO) were determined in serum and in intestinal homogenates.
Rats receiving rosiglitazone had higher body weight, whereas large intestine weight/length ratio was lower; histology showed fewer inflammatory markers. Rats receiving TNBS and TNBS along with BADGE had more intensive inflammatory changes. Rosiglitazone alone decreased expression of IL-6; used with TNBS it decreased expression of MPO in intestinal tissue, yet did not increase the expression of IL-10. Decreased levels of MPO indicate reduced neutrophil-dependent immune response. The antagonist of PPAR-γ increased IL-6 in serum and decreased IL-10 in intestinal homogenates. Bisphenol A diglycidyl ether administrated to healthy animals increases serum IL-6 levels.
Rosiglitazone inhibits experimental inflammation; administration of its selective antagonist abolishes this protective influence. Rosiglitazone inhibits expression of proinflammatory IL-6 and does not affect IL-10. Agonists of PPARs-γ are possibilities for inflammatory bowel disease prevention. Exogenous substances blocking PPARs-γ may contribute to development or relapse of nonspecific inflammatory bowel diseases.
本研究旨在确定过氧化物酶体增殖物激活受体γ（PPAR-γ）配体影响大鼠实验性结肠炎病程的机制。
材料/方法：通过单次直肠给予 2,4,6-三硝基苯磺酸（TNBS）诱导 Wistar 大鼠炎症。腹腔内给予 PPARγ 拮抗剂双酚 A 二缩水甘油醚（BADGE），120mg/kg，每两天 4 次。通过胃管给予罗格列酮 8mg/kg，每天 4 次。每天测量体重。处死动物后，称重大肠组织，用于组织病理学和免疫酶检测。在血清和肠匀浆中测定白细胞介素 6（IL-6）、白细胞介素 10（IL-10）和髓过氧化物酶（MPO）的水平。
给予罗格列酮的大鼠体重较高，而大肠重量/长度比较低；组织学显示炎症标志物较少。单独给予 TNBS 或 TNBS 联合 BADGE 的大鼠炎症变化更严重。罗格列酮单独降低 IL-6 的表达；与 TNBS 一起使用时，降低肠组织中的 MPO 表达，但不增加 IL-10 的表达。MPO 水平降低表明中性粒细胞依赖性免疫反应减少。PPAR-γ 拮抗剂增加血清中 IL-6 的水平，降低肠匀浆中 IL-10 的水平。在健康动物中给予 BADGE 可增加血清中 IL-6 的水平。
罗格列酮抑制实验性炎症；其选择性拮抗剂的给药会消除这种保护作用。罗格列酮抑制促炎 IL-6 的表达，不影响 IL-10。PPAR-γ 激动剂可能用于预防炎症性肠病。外源性物质阻断 PPAR-γ 可能导致非特异性炎症性肠病的发展或复发。
