Department of Gastroenterology, Medical University of Lublin, Lublin, Poland.
J Physiol Pharmacol. 2010 Dec;61(6):683-93.
PPAR-γ plays a role in the development of immune response, particularly in inflammation. The inflammatory reaction may be stimulated or suppressed by the presence of PPAR ligands. Some researchers suggest positive influence of the PPAR-γ agonist on suppression of the intestinal inflammatory process, yet there has not been much evidence showing that the antagonist of PPAR-γ can affect the inflammatory process. The aim of the present study was to define the mechanism by which PPAR-γ ligands affect the course of experimentally induced colitis in rats. Colitis was induced in rats by rectal administration of TNBS (trinitrobenzene sulfonate). Rosiglitazone was administrated to animals at the dose of 8 mg/kg four times via an intra-gastric probe. Biphenol-A-diglicydyl ether (BADGE) was administrated intraperitoneally at the dose of 120 mg/kg, three times every second day. One group of animals received rosiglitazone together with BADGE before the induction of inflammation. Histological and ELISA examinations of large intestine samples were performed. Levels of IL-1β, IL-6, TNF-α cytokines were determined in serum and homogenates. Rats exposed to rosiglitazone had higher body weight yet lower large intestine weight. Histological findings showed less ulceration, lower expression of crypts' loss and smaller oedema. Animals, which did not receive rosiglitazone, and those receiving it together with BADGE, developed more severe inflammatory changes. Rosiglitazone decreased the expression of inflammatory cytokines, such as IL-6 and TNF-α, both in serum and in intestinal homogenates. BADGE used with TNBS did not increase the expression of inflammatory cytokines; however, applied together with rosiglitazone, it caused inflammation similar to that observed among rats with experimentally induced colitis. Rosiglitazone reduces inflammation by decreasing the expression of IL-6 and TNF-α. BADGE administered with rosiglitazone blocks the activity of PPAR-γ and abolishes the protective effects of PPAR-γ agonist.
过氧化物酶体增殖物激活受体-γ（PPAR-γ）在免疫反应的发展中发挥作用，特别是在炎症中。PPAR 配体的存在可能会刺激或抑制炎症反应。一些研究人员认为，PPAR-γ 激动剂对抑制肠道炎症过程有积极影响，但没有太多证据表明 PPAR-γ 的拮抗剂可以影响炎症过程。本研究旨在确定 PPAR-γ 配体影响大鼠实验性结肠炎病程的机制。通过直肠给予三硝基苯磺酸（TNBS）诱导大鼠结肠炎。罗格列酮以 8mg/kg 的剂量通过胃内探头给药，共给药 4 次。双酚 A 双缩水甘油醚（BADGE）以 120mg/kg 的剂量，每两天腹腔内给药 3 次。一组动物在炎症诱导前同时给予罗格列酮和 BADGE。对大肠样本进行组织学和 ELISA 检查。在血清和匀浆中测定白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平。暴露于罗格列酮的大鼠体重增加，但大肠重量降低。组织学发现溃疡减轻，隐窝丢失表达减少，水肿较小。未接受罗格列酮和接受罗格列酮与 BADGE 治疗的动物炎症变化更为严重。罗格列酮降低了血清和肠匀浆中炎症细胞因子（如 IL-6 和 TNF-α）的表达。与 TNBS 一起使用 BADGE 并未增加炎症细胞因子的表达；然而，与罗格列酮一起应用时，它会导致类似于实验性结肠炎大鼠观察到的炎症。罗格列酮通过降低 IL-6 和 TNF-α 的表达来减轻炎症。与罗格列酮一起给予 BADGE 会阻断 PPAR-γ 的活性，并消除 PPAR-γ 激动剂的保护作用。
