血管紧张素1—7对高糖诱导人肾小管上皮细胞转分化的影响及其机制

Effect of angiotensin 1-7 on human renal proximal tubular epithelial cell transdifferentiationinduced by high glucose and its mechanism

目的研究血管紧张素1-7（Ang1-7）对高糖诱导人肾小管上皮细胞（HK-2）转分化的影响及其可能机制。方法培养HK一2细胞分组如下：对照组（N组）、高糖组（H组）、高糖＋Ang 1-7组（A组）、高糖＋Ang1-7＋A779组（D组）、高糖＋吡格列酮组（P组）。Western印迹检测各组HK一2细胞过氧化物酶体增殖物激活受体γ（PPAR-1）及α平滑肌肌动蛋白（α-SMA）的蛋白表达；实时定量PCR检测HK-2细胞PPAR-1及仅-SMA的mRNA表达；免疫荧光检测d．SMA表达。结果Ang1．7可上调高糖刺激下HK-2细胞PPAR．1蛋白及mRNA表达（P〈0．05）；抑制高糖刺激的α-SMA蛋白及mRNA表达（P〈0．05）。这种作用与PPAR-1激动剂吡格列酮类似。给予Mas受体抑制剂A779后，Angl-7的上述作用可被部分抑制。结论Ang1-7在体外可通过上调PPAR．1表达，从而部分抑制高糖诱导的α-SMA表达，实现其抑制转分化的作用，而这种作用部分通过Mas受体所介导。

Objective To investigate the effect of angiotensin 1-7 （Ang 1-7） on renal proximal tubular epithelial cell （HK-2） transdifferentiation induced by high glucose. Methods All the raised HK-2 ceils were divided into 5 groups： normal control group, high glucose group, high glucose with Angl-7 group, high glucose with Angl-7 and A779 group, high glucose with pioglitazone group. Expression of peroxisome proliferator activated receptor-γ（PPAR-γ） and a-smooth muscle actin （α-SMA） was detected by Western blotting, real-time PCR and immunofluorescence. Results The levels of PPAR-γ protein and mRNA in HK-2 cells were significantly increased after treatment with high glucose and Ang 1-7. Expression of α-SMA protein and mRNA was inhibited remarkably after treatment with high glucose and Aug 1-7. These effects of Ang 1-7 on HK-2 cells could be reversed by Mas receptor antagonist A779. Conclusion Ang 1-7 inhibits high glucose-induced expression of α-SMA in HK-2 cells, which is in part through the Mas.