Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
Free Radic Res. 2011 May;45(5):575-84. doi: 10.3109/10715762.2011.560149. Epub 2011 Mar 7.
The beneficial effects of telmisartan on Angiotensin (Ang)-II mediated oxidative stress and renal fibrosis in streptozotocin (STZ)-induced diabetic nephropathy (DN) were studied. Thirty mice were divided into normal (NG), STZ-induced diabetic (DG) and telmisartan-treated diabetic (TG) groups. Compared with NG mice, DG mice showed significant up-regulations of AT-1R, TGF-β1, p-p38MAPK, p-MAPKAPK-2, p-Akt, p47phox, p67phox, gp91phox protein and collagen-III and all of these were significantly reversed in TG mice. The down-regulated protein expression of Ang-(1-7) mas receptor, ACE-2, PPAR-γ and PGC-1α were observed in DG mice and a significant up-regulation effect of telmisartan has been seen in the TG mice. Furthermore, TG mice showed reduced expression of fibronectin, production of superoxide radical as well as renal hypertrophy and fibrosis when compared with DG mice. These findings suggest that Ang-II plays a significant role in DN and telmisartan would be beneficial in reducing oxidative stress and fibrosis in STZ-induced DN.
研究了替米沙坦对链脲佐菌素（STZ）诱导的糖尿病肾病（DN）中血管紧张素（Ang）-II 介导的氧化应激和肾纤维化的有益作用。将 30 只小鼠分为正常（NG）、STZ 诱导的糖尿病（DG）和替米沙坦治疗的糖尿病（TG）组。与 NG 组相比，DG 组 AT-1R、TGF-β1、p-p38MAPK、p-MAPKAPK-2、p-Akt、p47phox、p67phox、gp91phox 蛋白和胶原-III 的表达明显上调，而这些在 TG 组均明显逆转。DG 组 Ang-（1-7）mas 受体、ACE-2、PPAR-γ 和 PGC-1α 的蛋白表达下调，替米沙坦有明显的上调作用。此外，与 DG 组相比，TG 组的纤维连接蛋白表达减少，超氧自由基生成减少，肾肥大和纤维化减轻。这些发现表明 Ang-II 在 DN 中起重要作用，替米沙坦有益于减轻 STZ 诱导的 DN 中的氧化应激和纤维化。
