甘草酸二胺抗大鼠肾间质纤维化作用及其机制

Effect of Glycyrrhizin Acid on Renal Interstitial Fibrosis and Its Mechanism in Rats

目的探讨甘草酸二胺对肾间质纤维化的影响及其与TGF-β1/Smad2通路的关系。方法以Wistar大鼠单侧输尿管梗阻(UUO)为模型,在不同的时间点(7、14、28 d)处死动物,以Masson染色观察甘草酸二胺治疗前后梗阻侧肾小管的损害、肾间质纤维化指数;以免疫组化染色观察肾小管间质中转化生长因β1(TGF-β1)、Smad2信号蛋白及纤维连接蛋白(FN)等的表达情况;结果①随着梗阻时间的延长,肾小管损害、肾间质纤维化程度逐渐加重,呈时间依赖性(P<0.01);TGF-β1、Smad2、FN蛋白呈时间依赖性上调(P<0.01),均显著高于假手术组(P<0.01);TGF-β1与Smad2、Smad2与FN、TGF-β1与FN蛋白之间均呈显著正相关(r=0.987,r=0.992,r=0.981,均P<0.01)。②甘草酸二胺能改善UUO所致的肾间质纤维化程度(P<0.01),下调肾脏组织TGF-β1、Smad2、FN蛋白的表达(P<0.01)。结论甘草酸二胺能减轻UUO所致的肾间质纤维化损伤,其作用机制可能是通过抑制TGF-β1/Smads通路的激活,减少肾间质纤维连接蛋白的沉积,减轻肾间质的纤维化。

Objective To investigate the effects of glycyrrhizin acid （GA） on renal interstitial fibrosis and its mechanism. Methods Adult male Wistar rats were randomly divided into three groups： sham operated group （sham）; UUO group undergoing unilateral left ureteral obstruction; UUO and GA [20 mg/（kg· d）]-treated group （UUO＋GA）. Each group was subdivided into sub-groups （n= 6 for each） according to different interfered time as 7, 14, 28 days after the intervention and their left kidneys were taken out to undergo light microscopy by Masson staining to observe the renal interstitial fibrosis index. At the different time points, immunohistochemistry was used to detect the expression of TGF-β1, Smad2 and FN. Results The fibrosis index and renal tubule lesion in the UUO group were significantly increased as compared with sham group. The fibrosis index values in UUO＋GA group were significantly lower than in the UUO group （P〈0.01）. The expression of TGF-β1 and Smad2, Smad2 and FN,TGF β1 and FN protein all was significantly positively correlated （r= 0. 987, r：0. 992, r= 0. 981, all P〈0.01）. Conclusion GA may play a protective role in the kidney by inhibiting the overexpression of TGF-β1, Smad2 and decreasing the deposition of FN, which may consequently result in a decreased production of extracellular matrix, thus blocking the renal interstitial fibrosis lesion.