心肾综合征模型建立及肾素原受体信使核糖核酸表达的研究  

Establishment of Cardio-renal Syndrome and the mRNA Expression of Pro-renin Receptor in Experimental Rat's Model

作　　者：王蕾[1] 王梓[1] 郝迪[1] 李旭[1] 袁玲[1] 刘洪斌[1] 

机构地区：[1]天津市医药科学研究所,300020

出　　处：《中国循环杂志》2015年第9期895-899,共5页Chinese Circulation Journal

基　　金：国家自然科学基金青年科学基金项目(81202801);天津市中医药管理局中医;中西医结合专项(13180)

摘　　要：目的:通过"腹主动脉缩窄(CAA)合并肾脏急性缺血再灌注损伤(RIRI)"建立大鼠心肾综合征(CRS)模型,并观察肾素原受体信使核糖核酸的表达。方法:将42只Wistar大鼠按照体重随机分成4组(每组10只,造模过程中死亡2只):假手术组、CAA组、RIRI组、CAA+RIRI组。术后观察16周。酶联免疫法测定血清B型利钠肽(BNP),苦味酸法测定血肌酐(Cr),酶偶联速率法测定血清尿素氮(BUN),放射免疫法测定血浆肾素活性、血管紧张素-Ⅰ(Ang-Ⅰ)和Ang-Ⅱ、醛固酮含量;小动物超声心动图监测大鼠心脏舒张末期室间隔厚度(IVS)、舒张末期左心室后壁厚度(LVPW)、左心室射血分数(LVEF);记录心室重量指数、全心重量指数、肾脏重量指数,苏木素-伊红(HE)染色观察心肌、肾脏组织病理变化;荧光定量聚合酶链式反应法测定心室肌、肾脏组织肾素原受体信使核糖核酸表达。结果:CAA、RIRI、CAA+RIRI三组血清BNP均较假手术组明显升高(P<0.05);CAA+RIRI组血清Cr、BUN较CAA组显著升高(P<0.01),血浆醛固酮含量较假手术组和RIRI组均明显升高(P均<0.05);CAA+RIRI组的肾素活性较CAA组明显升高(P<0.05),但三个术式组血浆Ang-Ⅰ、Ang-Ⅱ无明显升高(P>0.05)。CAA+RIRI组IVS和LVEF变化程度较CAA组更明显(P均<0.01),CAA+RIRI组心室肥厚较RIRI组明显(P<0.05)。CAA+RIRI组心室和全心重量明显高于RIRI组(P<0.05),HE染色可见心肌细胞束的间隙稍增宽;左肾指数减小程度最明显,肾小管重度萎缩,部分肾小球萎缩。荧光定量聚合酶链式反应结果显示,假手术组大鼠心室肌和肾脏组织中均有肾素原受体表达,CAA、RIRI、CAA+RIRI三组大鼠肾素原受体表达均较假手术组减弱。结论:CAA+RIRI复合术式对心肌和肾脏同时构成损伤,损伤程度较CAA或RIRI单一术式更严重,手术方法可控性好、一致性高。该方法为肾素原受体用于CRS的治疗新途径研究提供了方法学参考。Objective： To establish the cardio-renal syndrome （CRS） model by coarctation of abdominal aorta （CAA） with renal ischemia reperfusion injury （RIRI）, and to observe the mRNA expression of pro-renin receptor [（P）RR] in experimental rats. Methods： A total of 42 Wistar rats were randomly divided into 4 groups： Sham group, CAA group, RIRI group and CAA＋RIRI group, n=10 in each group, 2 rats died during the modeling and all animals were treated for 16 weeks. Blood levels of BNP, creatinine （Cr）, urea nitrogen （BUN）, the activity of rennin, the contents of angiotensin-I （AT-I）, AT-II and aldosterone were examined by laboratory test. The diastolic end inter-ventricular septum thickness （DEIVST）, DELVPT, LVEF, ventricular weight index （VWI） and cardiac weight index were detected by small animal echocardiography. The histological changes of myocardium and kidney tissue were measured by HE staining, and the mRNA expressions of pro-renin receptor in myocardium and kidney tissues were measured by RT-PCR. Results： Compared with Sham group, blood levels of BNP were increased in the other 3 groups, P〈0.05; compared with CAA group, CAA＋RIRI group had increased levels of Cr and BUN, P〈0.01; compared with Sham group and RIRI group, CAA＋RIRI group showed increased blood level of aldosterone, P〈0.05. Compared with CAA group, CAA＋RIRI group presented increased rennin activity, P〈0.05. Blood levels of AT-Ⅰ and AT-Ⅱ were not significantly increased among 3 operation groups, P〉0.05. Compared with CAA group, CAA＋RIRI group had more obvious changes of DEIVST and LVEF, P〈0.01. Compared with RIRI group, CAA＋RIRI group had more obvious ventricular hypertrophy, higher VWI and cardiac weight index, all P〈0.05. HE staining presented that CAA＋RIRI group had broadening of myocardial cell bundle space, decreased left renal index, severe tubular atrophy and partial glomerular atrophy. RT-PCR demonstrated that compared with Sham group, the mRNA expressions of pro-renin recep

关 键 词：肾素原受体 心肾综合征 肾脏急性缺血再灌注损伤 腹主动脉缩窄 

分 类 号：R54[医药卫生—心血管疾病]