ACE2内源性激动剂DIZE对糖尿病肾病大鼠的保护作用

发布时间：2019-04-21 11:01

【摘要】：目的:观察血管紧张素转换酶2(ACE2)内源性激动剂乙酰甘氨酸重氮氨苯脒(DIZE)对糖尿病肾病(DN)大鼠的保护作用。方法:30只Wistar大鼠随机分为正常对照组(NC组)、DN组和DIZE处理组(DIZE组)。DN组与DIZE组一次性腹腔注射链脲佐菌素(65 mg/kg)建立糖尿病模型,12周后糖尿病肾病大鼠模型建立后给予DIZE 15 mg·kg~(-1)·d~(-1)或等量生理盐水皮下注射4周处理。16周末称量体重和肾重,计算肾质量体质量比(KW/BW),收集血、尿标本,检测血糖(GLU)、24 h尿蛋白(24UP)及血清肌酐(SCr)等指标。通过PAS染色观察各组肾脏病理变化;ELISA法检测大鼠AngⅡ、Ang-(1-7)、TGF-β1及VCAM-1水平的变化;通过免疫组化观察collagenⅠ和FN蛋白表达的变化;利用实时荧光定量PCR(RT-qPCR)技术检测大鼠肾组织collagenⅠ和FN mRNA含量的变化;Western blot观察各组大鼠ACE2蛋白表达的变化。结果:DIZE显著提高了糖尿病大鼠ACE2的表达(P0.05),降低了糖尿病大鼠血浆AngⅡ含量(P0.05),提高了Ang-(1-7)的水平(P0.05)。与NC组大鼠相比,DN组与DIZE组大鼠的24UP、SCr和KW/BW明显升高(P0.05),collagenⅠ和FN mRNA水平及蛋白表达量增加,肾脏组织TGF-β1及VCAM-1明显上升(P0.05)。DIZE组与DN组大鼠相比,24UP和SCr水平降低(P0.05),GLU和KW/BW无明显差异,collagenⅠ和FN mRNA含量及蛋白表达量减少,肾脏组织TGF-β1及VCAM-1水平降低(P0.05)。结论:ACE2内源性激动剂DIZE显著提高了ACE2的活性,增加了Ang-(1-7)的含量,从而降低了肾脏纤维化及炎症水平,并对糖尿病肾病大鼠起到保护性作用。
[Abstract]:Aim: to observe the protective effect of angiotensin converting enzyme 2 (ACE2) endogenous agonist acetylglycine diazapamidine (DIZE) on diabetic nephropathy (DN) rats. Methods: 30 Wistar rats were randomly divided into two groups: normal control group (NC group,), DN group) and DIZE treated group (DIZE group,). DN group) and DIZE group, which were treated with streptozotocin (65 mg/kg) intraperitoneally, and the diabetic model was established by intraperitoneal injection of 65 mg/kg. After 12 weeks, diabetic nephropathy rats were treated with DIZE 15 mg kg~ (- 1) d ~ (- 1) or normal saline for 4 weeks. At the end of 16 weeks, the weight and kidney weight were measured, and the body mass ratio (KW/BW) of kidney was calculated. Blood and urine samples were collected to detect blood glucose (GLU), 24 h urine protein (24UP) and serum creatinine (SCr). The pathological changes of kidney were observed by PAS staining, the levels of Ang 鈪，

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