转化生长因子-β_1在自发性高血压大鼠肾脏的表达及与肾间质纤维化的关系

Expression of TGF-β_1 in Kidney of Spontaneously Hypertensive Rats(SHR) and Its Role in Renal Fibrosis

目的 探讨转化生长因子 - β1(TGF - β1)在自发性高血压大鼠 (SHR)肾间质的沉积及其与肾间质纤维化的关系和培哚普利高血压肾间质纤维化的治疗作用。方法 SHR大鼠随机分为高血压组和治疗组 ,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在三组肾间质的沉积 ;半定量逆转录 -聚合酶链反应观察TGF - β1mRNA在三组肾脏的表达。结果 三组血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 (P <0 0 1orP <0 0 5 ) ,培哚普利能明显减少Ⅰ、Ⅲ型胶原及TGF - β1的沉积 ,显著降低TGF - β1mRNA的表达 (P <0 0 1orP <0 0 5 ) ;Ⅰ、Ⅲ型胶原的表达与肾间质TGF - β1的表达呈正相关 (r分别为 0 734、0 76 2 ,P <0 0 1) ,与血清中TGF - β1无关 (r分别为 0 0 6 9、0 180 ,P >0 0 5 )。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。培哚普利可能通过减少局部TGF - β1表达 ,来减轻肾间质纤维化。

Objective To study the expression of transforming growth factor-β_1 in kidney in SHR and its role in renal fibrosis and the effects of perindopril on the renal fibrosis. Methods Seventeen SHR of nine weeks of age were randomly assigned to control SHR(vehicle once daily,n =10)or T-SHR(perindopril,4mg·kg -1 ·d -1 ,PO,n =7). WKY( n =7) rats were used as control. After ten weeks,the serum concentration of TGF-β_1was examed by ELISA. Immunohistochemistry was applied to measured collagen Ⅰ,Ⅲ and TGF-β_1 in the renal interstitium;expression of TGF-β_1 mRNA in the kidney was analyzed by RT-PCR. Results In SHR,kidney weight/body weight(KW/BW)increased significantly. KW/BW was significantly decreased by perindopril. There were no significant difference in serum TGF-β_1 levels among the three groups( P >0.05). Immunohistochemistry studies revealed significant interstitial accumulation of collagens Ⅰ,Ⅲ and TGF-β_1 in SHR as compared with those of WKY rat ( P <0.01 or P <0.05). These changes in SHR were significantly attenuated by perindopril. Farther-more,perindopril substantially lower the over-expression of TGF-β_1 mRNA of SHR( P <0.01). The expression of collagens Ⅰ,Ⅲ in renal interstitum was correlated with the accumulation of TGF-β_1 in renal( P <0.01),while not related with the serum concentration of TGF-β_1( P >0.05). Conclusion The renal tubulointerstitial fibrosis of SHR was most likely mediated by an increased level of TGF-β_1 in renal tissue. Perindopril decrease the expression of TGF-β_1 ameliorate tubulointerstitial fibrosis.