缬沙坦对腹主动脉缩窄大鼠肾脏的保护

Renal protective effect of valsartan in rats with constricted abdominal aorta

目的 观察缬沙坦对腹主动脉缩窄（AAC）大鼠肾功能及肾间质纤维化的影响，并探讨其作用机制。方法 选择AAC术后的24只雄性SD大鼠，将其随机分为3组（对照组、低剂量缬沙坦组、高剂量缬沙坦组），另选8只作为假手术组。治疗10周后，测各组大鼠颈动脉压、尿微量白蛋白（mAlb）、内生肌酐清除率（Ccr）；使用Masson染色评估肾间质纤维化，放射免疫法检测血浆及肾脏血管紧张素（AngⅡ）的浓度，免疫组化法检测肾脏结缔组织生长因子（CTGF）的表达。结果与假手术组比较，对照组颈动脉压、。肾间质纤维化程度、尿mAlb、血浆及肾脏AngⅡ、CTGF表达水平均显著增高，而Ccr水平显著降低（P〈0．01）；与对照组比较，高剂量缬沙坦组颈动脉压、肾间质纤维化程度、尿mAlb、肾脏CTGF表达均明显下降，Ccr水平显著升高（P〈0．01），而低剂量缬沙坦组颈动脉压无明显变化，但其他指标明显优于对照组（P〈0．05或P〈0．01）。结论 缬沙坦可以有效地抑制AAC大鼠肾间质纤维化、改善肾功能，其作用机制可能与阻滞肾脏AngⅡ与AT1受体结合，CTGF的表达下调有关。

Objective After establishing the model of experimental hypertensive rats by abdominal aorta constriction （AAC）, to investigate the effect of angiotensin 11 type 1（AT1） receptor antagonist valsartan on renal interstitial fibrosis and renal function in AAC rats, and to explore the mechanisms. Method After suprarenal abdominal aorta constriction, 24 male SD rats were randomly divided into three groups： AAC control group; AAC-low dose valsartan treatment group and AAC high dose valsartan treatment group. Each group contained 8 rats. Eight sham-operated rats served as controis. After 10 weeks of therapy, the rats were sacrificed. The carotid arterial pressure, urinary mieroalbumin（mALB）, and endogenous creatinine clearance rate （Ccr） were measured. Concentration of angiotensin Ⅱ （AngⅡ ） in plasma and renal tissue were determined with radioimmunoassay. Kidney tissue of all groups was evaluated with special Masson＇s trichrome staining for the degree of renal interstitial fibrosis. The expression of connective tissue growth factor （CTGF） in kidneys was assessed by immunohistochemical method. Results Compared with sham operated rats, carotid arterial pressure, urinary mALB, Ang 1I in plasma and renal tissue , the degree of renal interstitial fibrosis and the expression of CTGF were signifie.antly increased in AAC control group（all P〈0. 01）, Ccr was decreased in this group （P〈0. 01） . Compared with AAC control group, carotid arterial pressure, urinary mALB, the degree of renal interstitial fibrosis and the expression of CTGF were significantly decreased in high dose valsartan treatment group（all P〈0. 01）, and Ccr was increased （P〈0. 01）. There was no significant difference in carotid arterial pressure between AAC control group and low dose valsartan treatment group（P2〉0, 05）, but other parameters in the latter were significantly ameliorated compared with the former（P〈0. 05 or P〈0. 01）. Conclusions Valsartan is effective in suppressing renal interstitial fibrosis and improving renal function. The proposed mechanism of this protective effect is the blockade of AT1 receptor and the down-regulation of CTGF expression.