黄芪当归合剂对梗阻性肾病大鼠肾间质纤维化的防治作用

Preventive and theraputic effects of astragalus and angelica mixture on renal tubulointerstitial fibrosis after unilateral ureteral obstruction in rats

目的 :研究黄芪当归合剂 (A&A)对梗阻性肾病大鼠肾小管间质纤维化的防治作用 ,探讨其抗纤维化作用的可能机制。方法 :采用单侧输尿管梗阻 (UUO)诱导肾间质纤维化的动物模型 ,以目前公认具有肾脏保护作用的血管紧张素转换酶抑制剂 (ACEI)作为阳性对照 ,将大鼠随机分为假手术组 (Sham)、模型组 (UUO)、黄芪当归合剂组 (A&A)、依那普利组 (ACEI) ,术后第 1 0天处死大鼠 ,收集血清测定肌酐、尿素氮水平 ,肾组织用Masson染色后进行图像分析评定各组肾小管间质损害程度 ,免疫组化半定量检测各组肾间质的α 平滑肌肌动蛋白 (α SMA)、转化生长因子 β1 (TGF β1 )、纤维连接蛋白 (FN)和层粘连蛋白 (LN)的表达。结果 :UUO组的肾小管间质损伤指数及α SMA、TGF β1 、FN和LN的表达明显高于Sham组 ,肾小管间质损伤指数与肾间质的α SMA、TGF β1 、FN和LN的表达均呈正相关关系。A&A组、ACEI组的肾小管间质损伤指数及α SMA、TGF β1 、FN和LN的表达均明显低于UUO组 ;两治疗组间比较 ,A&A对TGF β1 表达的抑制作用弱于依那普利的作用 ,而其余各指标差异无显著性。结论 :在单侧输尿管梗阻诱导的肾间质纤维化大鼠模型中 ,中药复方A&A的防治作用与ACEI相似 ,可能是通过减少肾间质肌成纤维细胞的数量、抑制TGF β1

Objective: To investigate the preventive and theraputic effects of Astragalus and Angelica mixture(A&A)on renal tubulointerstitial fibrosis after unilateral ureteral obstruction(UUO)in rats and their mechanisms. Methods: UUO rats were randomly divided into Sham, UUO, A&A or ACEI groups. A&A, ACEI or the same amount of water was administered by gavage beginning 24 hours before UUO preparation and continued through ten days after UUO. Sera and the kidney tissues were collected from each group on the tenth day. Scr and BUN were measured. Trichrome staining, measurement of tubulo interstitial damage index and immunohistochemical studies localizing α smooth muscle actin(α SMA), TGF β 1, fibronectin(FN), laminin(LN)were carried out. Results: In UUO rats, the tubular interstitial damage index, the expressions of α SMA, TGF β 1, FN and LN were all increased compared with those of Sham group. The tubulo interstitial damage index had positive correlation with expressions of α SMA, TGF β 1, FN and LN. A&A significantly ameliorated deterioration of renal function, tubulo interstitial damage index and inhibited the over expressions of α SMA, TGF β 1, FN and LN in UUO rats. These anti fibrotic effects were similar to those affected by ACEI. Conclusion: In renal interstitial fibrosis induced UUO rats, A&A retard the progression of renal fibrosis and renal function deterioration by inhibiting myofibroblasts and suppressing TGF β 1 expression, which may consequently result in a decreased production of extracellular matrix.