参附强心丸增强PRR/AQP2的表达对大鼠心肾综合征的影响

Effects of Shenfu Qiangxin Pills on rats with cardiorenal syndrome by enhancing the expression of PRR/AQP2

目的探讨参附强心丸对心肾综合征模型大鼠心、肾、脑组织中肾素原受体(PRR)/水通道蛋白(AQP2)表达的相互影响,为其治疗心肾综合征提供可能的作用机制。方法采用腹主动脉缩窄合并肾脏急性缺血再灌注的方法建立心肾综合征大鼠模型,除假手术组外,于术后8周将模型大鼠随机分为4组:模型组、、柄区肽10 mg/kg组、参附强心丸13.2 g生药/kg和6.6g生药/kg组。检测血清中肌酐(Cr)、尿素氮(BUN)和总三碘甲状腺原氨酸(T3)、总甲状腺激素(T4)、甲状腺刺激激素(TSH);并计算心室指数和左肾指数;采用免疫荧光检测心、肾及下丘脑中PRR、AQP2蛋白的表达。结果与模型组比较,参附强心丸13.2 g/kg组的Cr、BUN水平均明显降低(P<0.01),T3水平增加显著(P<0.01),大鼠全心指数、心室指数均显著减小(P<0.01),心室肌、肾脏PRR表达明显增强。结论参附强心丸不仅能改善心肌和肾脏功能,还可升高甲状腺系统的激素分泌水平,从而延缓心肾衰竭终末端病变进程,并证实了该药调控PRR与AQP2在下丘脑中同位点的共表达特点,对心肾综合征治疗机制研究具有的重要意义。

Objective To investigate the effect of Shenfu Qiangxin Pills in regulating the expression of renin proreceptor(PRR)and water channel protein(AQP2)in rats with cardiorenal syndrome,so as to provide a basis for further elucidation of the mechanism.Methods Rat model of cardiorenal syndrome was induced by abdominal aortic coarctation with acute renal ischemia reperfusion.After operation,except the sham operation group,the rats with cardiorenal syndrome were randomly divided into four groups:model group,Shenfu Qiangxin Pills 13.2 and 6.6 g crude drug/kg groups,and handle region peptide 10 mg/kg group.Cr,BUN,T3,T4,and TSH in serum were detected.The ventricular index and left kidney index were calculated.The expressions of PRR and AQP2 proteins in heart,kidney,and hypothalamus were detected by immunofluorescence.Results Compared with the model group,Cr and BUN levels in the Shenfu Qiangxin Pills 13.2 g/kg group were significantly decreased(P<0.01),but T3 level was significantly increased(P<0.01).Compared with the model group,the ventricular index and left kidney index in the Shenfu Qiangxin Pills 13.2 g/kg group were significantly decreased(P<0.01).And PRR expression in ventricular muscle and kidney in the Shenfu Qiangxin Pills 13.2 g/kg group were significantly increased compared with the model group.Conclusion Shenfu Qiangxin Pills can not only improve cardiac and renal function,it also increases hormone levels in the thyroid system.It delayed the progression of end-terminal lesions in heart and kidney failure,and confirmed the co-expression of PRR and AQP2 in the hypothalamus,which has important significance for the study of the therapeutic mechanism of cardiorenal syndrome.