福辛普利和缬沙坦对自发性高血压模型鼠肾损害中的作用

The effects of fosinopril and valsartan on renal injury in spontaneously hypertensive rats

目的探讨福辛普利(Fosinopril)和缬沙坦(Valsartan)对自发性高血压模型鼠肾损害中的作用。方法 20只22周龄雄性SHR,随机分为高血压组(SHR组)、福辛普利组(Fos组)、缬沙坦组(Val组)和福辛普利+缬沙坦组(Fos+Val组),22周龄雄性Wistar-Kyoto大鼠(WKY组)5只为对照组。检测各组大鼠体重,尾动脉血压,24h尿蛋白定量,尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG酶),左肾/体重比值和血肌酐。HE及Masson染色,显微镜下观察肾脏病理改变。结果实验第8周(30周龄),SHR组收缩压明显高于WKY组,Fos组,Val组及Fos+Val组(P均<0.05),而Fos组,Val组及Fos+Val组收缩压与WKY组比较无统计学差异(P>0.05);Fos组,Val组及Fos+Val组大鼠血肌酐和尿NAG酶明显低于SHR组(P均<0.05),而实验前与实验第8周大鼠蛋白尿排泄量差值(△Upro)均高于SHR组(P<0.05)。SHR组大鼠肾脏出现高血压肾脏损害的病理特征,胶原沉积增多,经Fos和/或Val干预后,高血压引起的肾脏改变明显改善。结论福辛普利和缬沙坦均有保护肾功能、延缓高血压导致肾间质纤维化的作用,但两者联合应用较单一用药在自发性高血压模型鼠中并不产生更大的降低尿蛋白和肾脏保护作用。

Aim To investigate the effects of fosinopril and valsartan on renal injury in spontaneously hypertensive rats. Methods Twenty 22 week-old male SHRs rats were randomly divided into four groups each consisted of five： hypertensive （SHR） group,Fos group,Val group and Fos＋Val group; five 22 week-old male Wistar-Kyoto rats （WKY） as the control group. After 8 weeks,the body weigh,cuff-tail blood pressure,24 hours urinary protein （Upro） ,left renal weigh/body weigh ratio,urinary N-acetyl-13-D-glucosaminidase （NAGase） and serum creatinine （Scr） were measured; the pathological changes were viewed under light microscopy by HE and Masson. Results The blood pressure of rats in SHR group was significantly higher than those of the other four groups （P〈0.05）,while there was not significantly different in the WKY group,Fos group ,Val group and Fos＋Val group （P〉0.05）; the levels of Scr and urinary NAGase were lower,and the contrast of 24h Upro in pre- and post-experiment was significant in Fos grpup, Val group and Fos＋Val group as compared to SHR group （all P〈0.05）. In morphology,a typical pathological feature of hypertensive renal injure,and the increased collagen deposited in renal interstitial area,were observed in the renal of SHR group as compared to the control; but the hypertensive renal injury was ameliorated in Fos group,Val group and Fos＋Val group. Conclusions Both of fosinopril and valsartan possess effect on the protection of the kidney and retarding renal interstitial fibrosis induced by hypertension, while the effect of combination of fosinopril and valsattan is not more effective than using fosinopril or valsartan alone.