Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
J Biochem Mol Toxicol. 2013 Jul;27(7):378-87. doi: 10.1002/jbt.21500. Epub 2013 Jun 3.
Angiotensin-converting enzyme (ACE) is upregulated in the diabetic kidney and contributes to renal injury. This study investigates the possible beneficial effects of the ACE inhibitor (ACEI), enalapril and the AT1 receptor blocker (ARB), valsartan, on renal ACE expression, renal structure, and function in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were allocated into four groups: control, STZ-diabetic rats, and STZ-diabetic rats treated with either enalapril (10 mg/kg/day) or valsartan (50 mg/kg/day) for 8 weeks. Enalapril and valsartan reduced renal ACE mRNA and protein expression, Na(+) /K(+) -ATPase activity, oxidative stress, and serum transforming growth factor-β1 levels compared to the diabetic group. Both treatments normalized renal nitrate/nitrite levels and ameliorated the observed histopathological changes. In conclusion, ACE downregulation by ACEI and ARB indicates that angiotensin II upregulates ACE through AT1 receptor. Prevention of diabetes-induced changes in ACE expression and Na(+) /K(+) -ATPase activity could be a new explanation of the renoprotective effects of ACEIs and ARBs.
血管紧张素转换酶（ACE）在糖尿病肾脏中上调，并有助于肾脏损伤。本研究探讨了血管紧张素转换酶抑制剂（ACEI）依那普利和血管紧张素 II 受体阻滞剂（ARB）缬沙坦对链脲佐菌素（STZ）诱导的糖尿病大鼠肾脏 ACE 表达、肾脏结构和功能的可能有益影响。雄性 Wistar 大鼠分为四组：对照组、STZ 糖尿病大鼠组、以及接受依那普利（10mg/kg/天）或缬沙坦（50mg/kg/天）治疗 8 周的 STZ 糖尿病大鼠组。与糖尿病组相比，依那普利和缬沙坦降低了肾脏 ACE mRNA 和蛋白表达、Na(+) /K(+) -ATP 酶活性、氧化应激和血清转化生长因子-β1 水平。两种治疗均使肾脏硝酸盐/亚硝酸盐水平正常化，并改善了观察到的组织病理学变化。总之，ACEI 和 ARB 通过 ACE 下调表明血管紧张素 II 通过 AT1 受体上调 ACE。预防糖尿病诱导的 ACE 表达和 Na(+) /K(+) -ATP 酶活性变化可能是 ACEI 和 ARB 的肾脏保护作用的新解释。
