【摘要】：目的:觀察血管緊張素轉(zhuǎn)換酶2(ACE2)內(nèi)源性激動(dòng)劑乙酰甘氨酸重氮氨苯脒(DIZE)對(duì)糖尿病腎病(DN)大鼠的保護(hù)作用。方法:30只Wistar大鼠隨機(jī)分為正常對(duì)照組(NC組)、DN組和DIZE處理組(DIZE組)。DN組與DIZE組一次性腹腔注射鏈脲佐菌素(65 mg/kg)建立糖尿病模型,12周后糖尿病腎病大鼠模型建立后給予DIZE 15 mg·kg~(-1)·d~(-1)或等量生理鹽水皮下注射4周處理。16周末稱(chēng)量體重和腎重,計(jì)算腎質(zhì)量體質(zhì)量比(KW/BW),收集血、尿標(biāo)本,檢測(cè)血糖(GLU)、24 h尿蛋白(24UP)及血清肌酐(SCr)等指標(biāo)。通過(guò)PAS染色觀察各組腎臟病理變化;ELISA法檢測(cè)大鼠AngⅡ、Ang-(1-7)、TGF-β1及VCAM-1水平的變化;通過(guò)免疫組化觀察collagenⅠ和FN蛋白表達(dá)的變化;利用實(shí)時(shí)熒光定量PCR(RT-qPCR)技術(shù)檢測(cè)大鼠腎組織collagenⅠ和FN mRNA含量的變化;Western blot觀察各組大鼠ACE2蛋白表達(dá)的變化。結(jié)果:DIZE顯著提高了糖尿病大鼠ACE2的表達(dá)(P0.05),降低了糖尿病大鼠血漿AngⅡ含量(P0.05),提高了Ang-(1-7)的水平(P0.05)。與NC組大鼠相比,DN組與DIZE組大鼠的24UP、SCr和KW/BW明顯升高(P0.05),collagenⅠ和FN mRNA水平及蛋白表達(dá)量增加,腎臟組織TGF-β1及VCAM-1明顯上升(P0.05)。DIZE組與DN組大鼠相比,24UP和SCr水平降低(P0.05),GLU和KW/BW無(wú)明顯差異,collagenⅠ和FN mRNA含量及蛋白表達(dá)量減少,腎臟組織TGF-β1及VCAM-1水平降低(P0.05)。結(jié)論:ACE2內(nèi)源性激動(dòng)劑DIZE顯著提高了ACE2的活性,增加了Ang-(1-7)的含量,從而降低了腎臟纖維化及炎癥水平,并對(duì)糖尿病腎病大鼠起到保護(hù)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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