Institute of Nephrology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing City, Jiangsu Province 210008, China.
Exp Biol Med (Maywood). 2020 Jun;245(11):983-993. doi: 10.1177/1535370220919364. Epub 2020 May 14.
Our study provided new insight into the mechanism underlying the preservation of the peritoneum by valsartan. The results demonstrated that the mice receiving chronic high glucose (HG) peritoneal dialysis solution infusion showed a typical feature of peritoneal fibrosis (PF), as well as higher expression of α-smooth muscle actin (α-SMA) and collagen I. , HG increased the protein expression of α-SMA and collagen I in a dose-dependent manner, while valsartan significantly ameliorated these pathological changes. Interestingly, there was a parallel decrease in the activity of mammalian target of rapamycin complex 1 (mTORC1) and the protein expression levels of α-SMA and collagen I upon treatment with valsartan and . Moreover, the mTOR agonist MHY1485 reversed the downregulation of α-SMA and collagen I , even in the presence of valsartan. Altogether, our findings reported for the first time that valsartan exerts a protective effect against HG-induced PF by inhibiting the activity of the mTORC1 pathway.
我们的研究为缬沙坦保护腹膜的机制提供了新的见解。结果表明，接受慢性高葡萄糖（HG）腹膜透析液输注的小鼠表现出典型的腹膜纤维化（PF）特征，以及α-平滑肌肌动蛋白（α-SMA）和胶原 I 的表达增加。HG 以剂量依赖性方式增加 α-SMA 和胶原 I 的蛋白表达，而缬沙坦则显著改善了这些病理变化。有趣的是，缬沙坦处理后，哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1）的活性以及 α-SMA 和胶原 I 的蛋白表达水平呈平行下降。此外，mTOR 激动剂 MHY1485 逆转了 α-SMA 和胶原 I 的下调，即使存在缬沙坦也是如此。总之，我们的研究结果首次报道，缬沙坦通过抑制 mTORC1 通路的活性对 HG 诱导的 PF 发挥保护作用。
