PPARγ激活对糖基化终末产物引起的大鼠肾系膜细胞TGFβ及CTGF mRNA表达的影响.doc

文档介绍：PPARγ激活对糖基化终末产物引起的大鼠肾系膜细胞TGFβ及CTGF mRNA表达的影响
(作者:___________单位: ___________邮编: ___________)
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(Rosiglitazo