Angiotensin-Converting Enzyme (ACE) 2 Overexpression Ameliorates Glomerular Injury in a Rat Model of Diabetic Nephropathy: A Comparison with ACE Inhibition
Angiotensin-Converting Enzyme (ACE) 2 Overexpression Ameliorates Glomerular Injury in a Rat Model of Diabetic Nephropathy: A Comparison with ACE Inhibition
复制标题
DOI：
10.2119/molmed.2010.00111
复制
发表时间：
2011-01-01
影响因子：
5.7
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
--
作者：
Liu, Chun Xi;Hu, Qin;Zhang, Yun
血管紧张素转换酶（ACE）2在动物模型和糖尿病患者肾脏中表达减少，提示ACE 2参与糖尿病肾病。为探讨血管紧张素转换酶2（ACE 2）过表达、血管紧张素转换酶抑制剂（ACEI）或两者联合应用对糖尿病肾病的保护作用及其机制，将50只Wistar大鼠随机分为正常对照组和糖尿病模型组，正常对照组注射枸橼酸钠缓冲液，糖尿病模型组注射链脲佐菌素60 mg/kg。链脲佐菌素注射8周后，将糖尿病大鼠分为未治疗组、腺病毒（Ad）-ACE 2组、腺病毒-绿色荧光蛋白（GFP）组、苯那普利+ACEI组和Ad-ACE 2 + ACEI组。治疗4周后，检测各组大鼠的生理、生化、肾功能及形态学指标。在培养的肾小球系膜细胞中进行实验以检查ACE 2对细胞增殖、氧化应激和IV型胶原合成的影响。与Ad-GFP组相比，Ad-ACE 2组收缩压、尿白蛋白排泄、肌酐清除率、肾小球硬化指数和肾脏丙二醛水平降低;转化生长因子（TGF）-β 1、血管内皮生长因子（VEGF）和IV型胶原蛋白表达下调;肾脏超氧化物歧化酶活性升高。Ad-ACE 2和ACEI具有相似的效果，而Ad-ACE 2和ACEI联合使用没有提供额外的益处。ACE 2转染减弱血管紧张素II诱导的肾小球系膜细胞增殖、氧化应激和IV型胶原蛋白合成。总之，ACE 2发挥类似于ACEI治疗的肾保护作用。其机制可能与肾组织Ang Ⅱ水平降低、Ang-（1-7）水平升高和氧化应激抑制有关。(c)2011 Feinstein医学研究所，www.feinsteininstitute.org在线地址：http://www.molmed.org doi：10.2119/molmed.2010.00111
The reduced expression of angiotensin-converting enzyme (ACE) 2 in the kidneys of animal models and patients with diabetes suggests ACE2 involvement in diabetic nephrology. To explore the renoprotective effects of ACE2 overexpression, ACE inhibition (ACEI) or both on diabetic nephropathy and the potential mechanisms involved, 50 Wistar rats were randomly divided into a normal group that received an injection of sodium citrate buffer and a diabetic model group that received an injection of 60 mg/kg streptozotocin. Eight wks after streptozotocin injection, the diabetic rats were divided into no treatment group, adenoviral (Ad)-ACE2 group, Ad-green flurescent protein (GFP) group, ACEI group receiving benazepril and Ad-ACE2 + ACEI group. Four wks after treatment, physical, biochemical, and renal functional and morphological parameters were measured. An experiment in cultured glomerular mesangial cells was performed to examine the effects of ACE2 on cellular proliferation, oxidative stress and collagen IV synthesis. In comparison with the Ad-GFP group, the Ad-ACE2 group exhibited reduced systolic blood pressure, urinary albumin excretion, creatinine clearance, glomeruli sclerosis index and renal malondialdehyde level; downregulated transforming growth factor (TGF)-beta 1, vascular endothelial growth factor (VEGF) and collagen IV protein expression; and increased renal superoxide dismutase activity. Ad-ACE2 and ACEI had similar effects, whereas combined use of Ad-ACE2 and ACEI offered no additional benefits. ACE2 transfection attenuated angiotensin (Ang) II-induced glomerular mesangial cell proliferation, oxidative stress and collagen IV protein synthesis. In conclusion, ACE2 exerts a renoprotective effect similar to that of ACEI treatment. Decreased renal Ang II, increased renal Ang-(1-7) levels, and inhibited oxidative stress were the possible mechanisms involved. (c) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2010.00111