贝那普利和缬沙坦联合应用对肾组织中转化生长因子β_1的影响

The effect of combination treatment with benazepril and valsartan on transforming growth factor beta in renal tissues

目的 探讨贝那普利和缬沙坦联合应用对肾组织中转化生长因子 β1(TGF β1)影响。方法 6 0只SD大鼠随机均分为 5组 ,正常对照组 (A组 )和肾病组 (B、C、D、E组 )。对肾病组大鼠单侧肾脏切除 1周后行多柔比星尾静脉注射 ,建立肾小球硬化模型。之后 ,C、D两组分别给予贝那普利 6mg/ (kg·d)、缬沙坦 2 0mg/ (kg·d)灌胃 ,E组给予贝那普利 3mg/ (kg·d)、缬沙坦 10mg/ (kg·d)联合灌胃 ,12周后全部处死。观察尿蛋白、血生化及肾脏组织中TGF β1表达水平的变化。结果 1.E组尿蛋白第 5周起较B组明显降低 ,C、D两组第 7周起较B组明显降低。 2 .免疫组化显示 ,TGF β1在A组表达最少 ,B组表达最强。结论 在肾小球硬化模型中 ,贝那普利和缬沙坦具有相似的下调TGF β1表达的作用 。

Objective To observe the effects of the combination treatment with angiotensin converting enzgme inhibtor -benazepril and angiotensin Ⅱ type-Ⅰ receptor antagonist-valsartan on transforming growth factor beta (TGF-β 1) in renal tissues.Methods Sixty male Sprague -Dawley rats were randomly divided into 5 groups: normal control group (group A)and nephropathy groups (group B,C,D and E).The nephropathy groups were uninephrectomized and injected with adriamycin (5 mg/kg) through the tail vein 1 week after uninephrectomy.Group C and D were treated with benazepril[6 mg/(kg·d)] and valsartan[20 mg/(kg·d)] by gastric-perfusion every day,respectively.Group E were co-treated with benazepril(3 mg/kg·d)and valsartan(10 mg/kg·d) by gastric-perfusion every day.All rats were harvested at the 12th week.Twenty-four hours urinary protein excretion,serum biochemical value were examined.The expression of TGF-β1 in renal tissues was measured with immunohistochemical method.Results 1.The 24 hours urinary protein excretion was lower in co-treated group than that in untreated group from 5th week (P<0.05),while the proteinuria was lower in 2 monotherapy groups only after 5th week (P<0.01).2.The percentage of staining positive-cells was the highest in group B(P<0.01) and the lowest in group A both in intraglomerular and in tubulointerstitium (P<0.05).Conclusions These results suggest that the effects of benazepril and valsartan on TGF-β1 are very similar and there is a trend that combination of both agents is superior to monotherapy.