肾络通对肾间质纤维化实验大鼠肾小管上皮细胞转分化的影响

Effect of Shenluotong on tubular epithelialmyofibroblast transdifferentiation in rats with tubulointerstitial fibrosis

目的观察肾络通对肾间质纤维化实验大鼠肾小管上皮细胞转分化的影响。方法选用健康、雌性SD大鼠50只,用单侧输尿管结扎方法复制大鼠肾间质纤维化模型,将其随机分为缬沙坦组[予缬沙坦10 mg/(kg.d)经口灌服]、肾络通组[肾络通26 g/(kg.d)经口灌服]、肾络通加缬沙坦组[予缬沙坦10 mg/(kg.d)和肾络通26 g/(kg.d)经口灌服]与模型组[予等量0.9%氯化钠注射液经口灌服],并设假手术组,每组10只大鼠。行HE、Masson染色观察实验大鼠梗阻侧肾脏组织形态学改变,并用免疫组化及原为杂交方法检测实验大鼠梗阻侧肾脏α-平滑肌肌动蛋白(α-SMA)及角蛋白(CK)在蛋白或基因水平的表达。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(P<0.05),α-SMA的表达也增加(P<0.05),CK的表达明显减少(P<0.05)。各治疗组与模型组比较,病理损害减轻(P<0.05),α-SMA表达明显减少(P<0.05),CK表达明显增强(P<0.05),治疗各组间比较,肾络通加缬沙坦组优于缬沙坦组(P<0.05),其他各组间差异均无统计学意义(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,这可能与α-SMA蛋白及其mRNA的表达增加有关。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 tubular epithelialmyofibroblast transdifferentiation in rats with tubulointerstitial fibrosis. Methods The model of renal obstruction was established by unilateral ureteral obstruction （UUO） in rats and then the rats were divided into five groups, including UUO group, UUOV group[ treated with valsartan 10 mg/（ kg·d ） ], UUOS group[ treated with Shenluotong 26 g/（ kg· d ） ], UUOVS group[ treated with valsartan 10 mg/（kg· d ） and Shenluotong 26 g/（kg·d ） ] and sham - operation group. The morphological change of kidney tissue and protein or gene expressions of α-smooth muscular actin（ α- SMA）and cytokeratin（CK） in kidney tissue were observed. Results In UUO group and the different treatment groups there were different degrees of lesions of kidney, as compared with sham - operation group. The expression of α-SMA in kidney tissue was increased obviously while the expression of CK in kidney tissue was significantly decreased （ P 〈 0.05）. As compared with that in UUO group, the pathological lesion and expression of α-SMA decreased significantly in treatment groups, however, the expression of CK in kidney tissue were decreased（ P 〈 0. 05）. The comparison between different treatment groups showed that the expression of α- SMA and CK in UUOVS group was better than that in UUOV group（ P 〈 0.05）, but there was no signitieant differenee among other treatment groups（ P 〉 0. 05）. Conclusion After unilateral ureteral obstruction the different degas of pathologieal ehanges in kidney tissue ean be seen, which are related to the expression of α- SMA. Shenluotong and valsarten have an inhibitory effect. The combined use of both drugs is better than only use of one drug.