肾络通对肾间质纤维化实验大鼠病理及基质金属蛋白酶系统的影响

Effect of Shenluotong on pathology and system of MMP-1/TIMP-1 in rats with tubulointerstitial fibrosis

目的观察肾络通对实验大鼠肾间质纤维化的拮抗作用并探讨其作用机理。方法用单侧输尿管结扎方法复制大鼠肾梗阻模型,将其随机分为缬沙坦组、肾络通组、肾络通加缬沙坦组与模型组,并设假手术组。观察梗阻侧肾脏组织形态学改变、基质金属蛋白酶-1(MMP-1)及其基质金属蛋白酶抑制剂-1(TIMP-1)在蛋白及基因水平的表达并与假手术组比较。结果模型组及各治疗组与假手术组比较均呈现程度不同的病理损害,MMP-1、TIMP-1表达均有显著增高(P<0.05),且TIMP-1表达明显高于MMP-1表达。各治疗组与模型组比较,MMP-1表达无明显差异(P>0.05),TIMP-1表达却明显减少(P<0.05)。治疗各组间比较,TIMP-1表达肾络通加缬沙坦组明显低于缬沙坦组(P<0.05),其他组间均无明显差异(P>0.05)。结论输尿管梗阻后肾组织呈现程度不同的病理损害,可能与MMP-1/TIMP-1表达明显失衡有关。肾络通及缬沙坦对其有一定的抑制作用,且肾络通与缬沙坦联合用药,其作用比单一用药更强。

Objective To observe the effect of Shenluotong on tubulointerstitial fibrosis in rats and try to find the mechanism. Methods The model of renal obstruction was established by unilateral ureteral obstruction （UUO） in rats, and then divided them randomly into five groups, including UUOV group （ treated with Valsartan）, UUOS group （treated with Shenluotong）, UUOVS group （treated with Valsartan and Shenluotong）, UUO group and the sham-operation group. The morphological change of kidney tissue and the protein and gene expressions of MMP-1 and TIMP-1 were observed and compared with that of the sham-operation group. Results In UUO group and different treatment groups there were different degrees of lesions of kidney compared with the sham-operation group. The expressions of MMP-1 and TIMP- 1 in kidney tissue were increased obviously （P 〈 0. 05 ）, and the expression of TIMP-1 was higher than that of MMP-1. There was no significant difference in the expression of MMP-1 between different treatment groups and UUO group （P 〈 0. 05 ） , while the expression of TIMP-1 decreased significantly （ P 〈 0. 05）. The comparison between different treatment groups showed that the expression of TIMP-1 in UUOVS group was lower obviously than that in UUOV group （ P 〈 0. 05 ）, but there was no significant difference between other treatment groups （ P 〉 0.05 ）. Conclusion After＇ unilateral ureteral obstruction the different degrees of pathological changes in kidney tissue were seen, which was related to the unbalance of MMP-1/TIMP-1 expressions. Shenluotong and Valsartan have an inhibitory effect. The combined use of both drugs was better than only use of one drug.