厄贝沙坦对自发性高血压慢性肾功能衰竭大鼠肾功能的影响及机制研究

目的观察厄贝沙坦对自发性高血压大鼠慢性肾功能衰竭(SHR-CRF)模型肾功能的影响并探讨其机制。方法 SHR随机分为模型组及厄贝沙坦高、中、低剂量组,另设Wistar大鼠作为对照组。采用SHR进行5/6肾切除复制SHR-CRF模型。造模后予大鼠灌胃给药,连续8周。观察一般状况、血压,测定血液中尿素氮(BUN)、肌酐(Cr)浓度及尿液中尿蛋白(UP)、BUN、Cr、尿微量白蛋白(mALB)的浓度;采用荧光定量PCR测定肾转化生长因子-β_1(TGF-β_1)、转化生长因子-β受体Ⅰ(TGF-βRⅠ)、转化生长因子-β受体Ⅱ(TGF-βRⅡ)、Smad3 mRNA的表达。结果厄贝沙坦能显著改善SHR-CRF大鼠症状,降低血压(P<0.05),降低血液中BUN、Cr及尿液中UP、BUN、Cr、mALB浓度(P<0.05),降低肾组织TGF-β_1、TGF-βRⅠ、TGF-βRⅡ、Smad3表达。结论厄贝沙坦能降低SHR-CRF模型的血压、改善肾功能,与抑制肾脏TGF-β_1/Smad3信号通路的激活有关。

Effect of irbesartan on renal function in chronic renal failure of spontaneously hypertensive rats and its mechanism

Objective To investigate the effect of irbesartan on renal function in chronic renal failure of spontaneously hypertensive rats（SHR-CRF）and its mechanism.Methods SHR were randomly divided into four groups:the model group,irbesartan high,middle,and low group.Wistar rat was used as control group.The model of SHR-CRF rats were established by 5/6 nephrectomize in SHR rats.All groups were irrigated for 8 weeks.The general condition was recorded.The blood pressure was measured.The contents of urea nitrogen（BUN）,creatinine（Cr）in blood,and the contents of UP, BUN,Cr,microalbuminuria（mALB）in urine were tested.Fluorescence quantitative PCR（FQPCR）were used to examine the mRNA expression level of transformation growth factor-β₁（TGF-β₁）,transformation growth factor-p,receptorⅠ（TGF-βRI）, TGF-βRⅡand Smad3 of kidney.Results Irbesartan can markedly ameliorate the symptoms of SHR-CRF rats and reduce the blood pressure（P<0.05）.Irbesartan can reduce BUN,CRE concentration in blood（P<0.05）and UP,BUN, Cr,mALB concentration in urine（P<0.05）.Irbesartan can reduce renal tissue lesions.The expression of TGF-β,,TGF-βRⅠ, TGF-βRⅡ,Smad3 of renal decreased in irbesartan group.Conclusion Irbesartan can decrease the blood pressure and ameliorate renal function in SHR-CRF rats by inhibiting activation of TGF-β₁/Smad3 signal pathway in kidney.