培跺普利对高血压大鼠肾间质纤维化的治疗作用

Effect of perindopril on renal interstitial fibrosis of hypertension in rats

目的 :探讨培跺普利对高血压肾间质纤维化的抑制作用和TGF β1表达的影响。方法 :Spontaneouslyhypertensiverats (SHR)大鼠随机分为高血压组和培跺普利治疗组 ,Wistar Kyotorats(WKY)大鼠为对照组。ELISA法测血清TGF β1的浓度 ;免疫组织化学染色法检测Ⅰ ,Ⅲ型胶原和TGF β1在 3组肾间质的沉积 ;半定量逆转录 聚合酶链反应观察TGF β1mRNA在 3组肾脏的表达。结果 :3组血TGF β1浓度的差异无显著性 (P >0 .0 5 ) ;高血压组肾间质Ⅰ ,Ⅲ型胶原及TGF β1明显增加 (分别为P <0 .0 1,P <0 .0 5 ) ,培跺普利能明显减少Ⅰ ,Ⅲ型胶原及TGF β1的沉积 ,显著降低TGF β1mRNA的表达 (分别为P <0 .0 1,P <0 .0 5 ) ;Ⅰ ,Ⅲ型胶原的表达与肾间质TGF β1的表达呈正相关 (分别为r=0 .734,r=0 .76 2 ,P <0 .0 1)。结论 :肾脏局部的TGF β1参与了自发性高血压大鼠肾间质纤维化 ,培跺普利可通过减少肾脏局部的TGF β1的表达 。

Objective To explore the effect of perindopril on renal interstitial fibrosis of spontaneously hypertensive rats and on the expression of transforming growth factor-β 1.Methods Spontaneously hypertensive rats at the age of 9 weeks were randomly assigned to 2 groups:Spontaneously hypertensive rats (SHR , vehicle once daily, n=10)and Treament-SHR(T-SHR , perindopril,4 mg/(kg·d), per day PO,n=10). Wistar-Kyoto rats (WKY, n=7) were served as controls. After 10 weeks of treatment, the serum concentration of TGF-β 1, collagen typeⅠ, Ⅲ and TGF-β 1 in the renal interstitum and renal mRNA levels of TGF-β 1 were detected.Results There were no significant differences in the serum TGF-β 1 levels among the 3 groups (P>0.05). Immunohistochemical studies revealed a significant interstitial accumulation of collagens Ⅰ,Ⅲ and TGF-β 1 in SHR compared with those in WKY(P<0.01 or P< 0.05). These changes in SHR were significantly ameliorated by the administration of perindopril(P<0.01 or P< 0.05). In SHR, renal TGF-β 1 mRNA expression was increased significantly compared with that in WKY(P<0.01), but perindopril decreased it to the normal levels of WKY(P>0.05). The increased expression of TGF-β 1 was blocked by perindopril. The expressions of collagensⅠand Ⅲ in renal interstitum significantly correlated with the accumulation of TGF-β 1 in the renal (r=0.734,r=0.762,respectively; P< 0.01).Conclusion The tubulointerstitial fibrosis of spontaneously hypertensive rats is mediated by an increased level of TGF-β 1 in the renal tissue, and perindopril may decrease the expression of TGF-β 1 to ameliorate the tubulointerstitial fibrosis.