苯那普利和缬沙坦联合应用对肾病大鼠肾脏细胞周期调控的影响

目的：探讨苯那普利和缬沙坦联合应用对肾硬化大鼠肾脏细胞周期调控的影响。方法：55只SD大鼠分为5组,即对照组、模型组、苯那普利组、缬沙坦组及联合组。对模型组和三治疗组大鼠行单侧肾脏切除,1周后给予阿霉素（5mg/kg）尾静脉注射,建立肾小球硬化模型。自注射阿霉素后,苯那普利组和缬沙坦组分别给予苯那普利6mg.kg-1.d-1、缬沙坦20mg.kg-1.d-1灌胃,联合组给予苯那普利3mg.kg-1.d-1联合缬沙坦10mg.kg-1.d-1灌胃。12周后全部处死,检测肾脏周期素D1和P27的表达,计算阳性细胞所占的百分数。结果：周期素D1在苯那普利、缬沙坦、联合组较模型组明显减少（P均〈0.01）,而联合组与苯那普利、缬沙坦组之间无差异。P27在苯那普利、缬沙坦、联合组较模型组明显增高（P均〈0.01）,而联合组又高于苯那普利、缬沙坦两组（P均〈0.05）。P27与周期素D1均呈负相关。结论：苯那普利和缬沙坦均通过减少肾脏周期素D1和增加P27的表达延缓肾小球硬化,联合应用苯那普利和缬沙坦对P27的调控比单独应用作用更大。

Effects of Combination with Benazepril and Valsartan on Renal Cell Cycle Regulation in Nephrotic Rats

Objective:To study the effects of combination with benazepril and valsartan on renal cell cycle regulation in the kidney of nephrotic rats.Methods:Fifty-five male Sprague Dawley rats were divided into control group,model group,benazepril treated group,valsartan treated group and co-treated group.The rats from later four groups were cut off one side kidney and injected with adriamycin(5 mg/kg)through the tail vein one week after later.The rats from later three treated groups were respectively gastric-perfused with benazepril(6 mg/kg),valsartan(20 mg/kg),both benazepril(3 mg/kg)and valsartan(10 mg/kg)every day for 12 weeks.Immunohistochemistry was utilized to detect the expression of cyclin D1 and P27 in the kidney.Results:The expression of cyclin D1 in benazepril treated group,valsartan treated group and co-treated group was significantly decreased than that in model group(P<0.01,repectively),but there were no significant difference among three treated groups(P>0.05,respectively).The expression of P27 in three treatment groups was significantly increased than that in model group(P<0.01,repectively),while that in co-treated group was higher than that in benazepril treated group and valsartan treated group(P< 0.05,repectively).There was markedly negative correlation between P27 and cyclin D1.Conclusion:These results suggest that benazepril and valsartan ameliorate glomerulosclerosis by regulating renal cell cycle.The effect of combination treated with benazepril and valsartan in inducing P27 expression on renal cells is superior to monotherapy.