PPARγ激活对糖基化终末产物引起大鼠肾系膜细胞TGFβ及CTG.docVIP

PPARγ激活对糖基化终末产物引起大鼠肾系膜细胞TGFβ及CTG 　 作者：刘辉 于晓艳 魏海峰 石艳 苗春生 李才 邹颖刚 【摘要】 目的 观察过氧化物酶体增殖体激活受体γ(PPARγ)激活对糖基化终末产物(AGEs)引起的大鼠肾系膜细胞TGFβ及CTGF mRNA表达的影响。方法 体外培养正常大鼠肾系膜细胞，逆转录聚合酶链式反应(RTPCR)检测不同浓度AGEs(0～400 μg/ml1)及不同浓度PPAPγ)激活剂(罗格列酮)和PPARγ阻断剂(GW9662)对AGEs(100 μg/ml-1)引起的TGFβ及CTGF mRNA表达的影响。结果 给予PPARγ激活剂可明显减轻AGEs引起的大鼠系膜细胞TGFβ、CTGF mRNA的表达。结论 PPARγ激活剂可以明显减轻AGEs对系膜细胞TGFβ、CTGF mRNA的表达影响，从而改善肾小球细胞外基质积聚,在糖尿病时起到肾脏保护作用。 【关键词】 过氧化物酶体增殖体激活受体γ;糖尿病肾病; 糖基化终末产物;转化生长因子β;结缔组织生长因子 　　【Abstract】 Objective To investigate the role of peroxisome proliferatoractivated receptor(PPAR)γ activation on the expressions of TGFβ and CTGF mRNA in rat mesangial cells extenuation induced by advanced glycation end products (AGEs). Methods Rat mesangial cells were treated with AGEmodified bovine serum albumin or native bovine serum albumin. Normal mesangial cells without any treatments were as control. TGFβ and CTGF mRNA were analyzed by reverse transcriptasepolymerase chain reaction (RTPCR). The expressions of TGFβ and CTGF mRNA in mesangial cell induced by rosiglitazone (0～10 μmol/L) and the inhibitor of PPARγ(10 μmol/L) were tested with RTPCR. Results PPARγ activation relieved TGFβ and CTGF mRNA expressing induced by AGEs(0～400 mg/L) in mesangial cells. Conclusions PPARγ activation can relieve the expressions of TGFβ and CTGF mRNA in rat mesangial cells induced by AGEs，suggesting that PPARγ activation has a kidney protection in diabetic mellitus through ameliorating extracellular matrix accumulation. 　　【Key words】 Peroxisome proliferator activated receptorγ; Diabetic nephropathies; Glycosylation end products, Advanced; TGFβ;CTGF 　 糖尿病肾病(DN)的发病机制是以高血糖为启动因素所诱导的各种血管活性物质、生长因子、细胞介质等综合作用的结果，其中转化生长因子β(TGFβ)和结缔组织生长因子(CTGF)的作用尤其受到关注。持续高血糖状态下体内蛋白质能发生一系列非酶促糖基化反应，最后形成的糖基化终末产物(AGEs)在DN发生机制中具有重要意义〔1〕，AGEs可诱导TGFβ和CTGF等基因表达异常。过氧化物酶体增殖体激活受体γ(PPARγ)是核内受体转录因子超家族成员之一，在脂肪生成、胰岛素敏感性、细胞周期调节及细胞分化中起重要作用，抗糖尿病药物胰岛素增敏剂四氢噻唑烷二酮类药物 (TZDs)如罗格列酮(Rosiglitazone，RSG)是PPARγ的特异性激活剂。RSG不仅能减轻糖尿病肾小球细胞外基质合成，还能增加细胞外基质