核受体PPARγ在醛固酮诱导大鼠急性肾损伤中的作用研究  

Roles of nuclear receptor PPARγ in aldosterone-induced rat renal injury

作　　者：金国萍[1] 应利君[1] 童海明[2] 孟东亮[1] 屠国伟[3] 

机构地区：[1]绍兴市人民医院重症医学科,312000 [2]绍兴市人民医院检验科,312000 [3]复旦大学附属中山医院重症医学科

出　　处：《浙江医学》2015年第14期1196-1198,1208,共4页Zhejiang Medical Journal

摘　　要：目的探讨核受体过氧化物酶体增殖物激活受体γ(PPARγ)在醛固酮诱导急性肾脏损伤过程中的作用,以及其激活剂罗格列酮治疗肾损伤的可行性。方法将27只5周龄雄性SD大鼠切除右肾,手术2周后予1%氯化钠溶液饮水。按随机数字表法分为3组,每组9只:对照组予2%乙醇2ml皮下泵入,醛固酮组予2%乙醇2ml+醛固酮0.75μg/h皮下泵入,醛固酮+罗格列酮组予2%乙醇2ml+醛固酮0.75μg/h皮下泵入+罗格列酮0.1mg/(kg·d)皮下注射,给药时间5周。检测大鼠收缩压变化、尿蛋白水平、肾功能、肾组织学的改变以及核受体PPARγ表达水平的变化。结果与对照组比较,醛固酮组、醛固酮+罗格列酮组大鼠体重明显减轻,肾重、肾重/体重比明显增加,肌酐清除率明显下降(均P<0.05)。醛固酮组大鼠的SBP随着灌流时间的延长而不断增高,尿蛋白水平也明显增高,均高于对照组(均P<0.05);而罗格列酮对醛固酮引起的大鼠SBP升高没有明显影响,但对醛固酮造成尿蛋白的升高有明显的抑制作用。醛固酮组大鼠肾组织病理检查表现为严重的肾小球内细胞增生和硬化,肾小球出现纤维素样坏死,肾小管有明显扩张现象;而醛固酮+罗格列酮组大鼠肾损伤明显改善,主要表现在肾小球内细胞增生和硬化水平减少,纤维样坏死程度减轻,肾小管间质纤维化减轻。在醛固酮诱导的肾损伤中,核受体PPARγ及其在mRNA水平表达量较对照组均有明显的增高。结论核受体PPARγ在醛固酮诱导大鼠肾损伤中表达量明显升高,核受体PPARγ激活剂罗格列酮可以改善醛固酮诱导的大鼠肾损伤。Objective To investigate the roles of nuclear receptor PPAR~ in aldosterone-induced renal injury in uninephrectomized SD rats. Methods Twenty seven SD rats were uninephrectomized and 2 weeks after surgery the rats were randomly divided into 3 groups with 9 animals in each. The rats in 3 groups were given following treatment for 5 weeks, respec- tively： vehicle （2% Ethanol, SC）, aldosterone （2% Ethanol＋0.75μg/h, SC） or aldosterone （2% Ethanol＋0.75μg/h, SC） ＋ RPAR ago- nist rosiglitazone （Rosi） [0.1 mg/（kg.d）, SC], Systolic blood pressure （SBP）, urinary protein, renal function and renal morphologic changes were examined; and the expression PPAR mRNA and protein were all measured by Western blotting and real-time PCR, respectively. Results Compared with the control group, the groups of aldosterone and aldosterone ＋ Rosiglitazone showed de- creased body weight and creatinine clearance rate while the kidney weight and kidney weight/body weight ratio were significant- ly increased（P〈0.05）. Aldosterone-infused rats exhibited hypertension and proteinuria over time compared with the control group P〈0.05）. Rosigtitazone had no effect on the systolic blood pressure of the rats intervened by aldosterone, however, the protein- uria caused by aldosterone was significantly alleviated. The pathological examinations showed severe renal injury characterized by glomerular endothelial cell proliferation and sclerosis, gtomerular fibrinoid necrosis, and tubular ectasia in group of aldosterone. The group of aldosterone＋Rosiglitazone exhibited dramatically improved pathological changes above-mentioned. The expression level of PPAR protein and mRNA increased in kidney of rats treated by aldosterone compared with the control group. Conclusion The expression level of PPAR is increased in the injured renal tissue of rats, and the renal injury induced by aldosterone can be attenuated by PPAR agonist rosiglitazone.

关 键 词：醛固酮 肾脏损伤 过氧化物酶体增殖物激活受体Γ 罗格列酮 

分 类 号：R692[医药卫生—泌尿科学]