水飞蓟素对单侧输尿管结扎大鼠肾组织TGF-β1及TSP-1表达的影响

Effect of silymarin on expression of TGF-β1 and TSP-1 in renal tissues of UUO rats

目的 探讨水飞蓟素对肾间质纤维化的影响及其可能机制.方法 将36只雄性SD大鼠随机分为假手术组（C组）、模型组（M组）和水飞蓟素治疗组（S组）,各12只.对M组和S组大鼠建立单侧输尿管结扎（UUO）模型,C组仅分离左侧输尿管,未行结扎.S组大鼠给予水飞蓟素（50 mg/kg）灌胃.每组大鼠于术后第7、21天分别处死6只.观察各组大鼠肾组织病理学表现,采用RT-PCR方法检测各组大鼠肾组织转化生长因子β1（TGF-β1）和血小板反应蛋白1（TSP-1）mRNA表达水平.结果 术后第7天,M组大鼠肾组织出现肾小管明显扩张,偶见肾小管上皮细胞坏死、肾间质水肿、轻度纤维化,并有较多单个核细胞浸润;第21天,肾小管扩张进一步加重,并出现肾小管上皮细胞大量坏死,并可见肾间质大量胶原纤维组织增生,伴大量炎症细胞浸润;S组较M组肾组织损伤减轻,肾小管间质损伤指数降低（P〈 0.05）.术后第7、21天,M组TGF-β1和TSP-1 mRNA表达均较C组升高（P〈0.01）,S组TGF-β1和TSP-1 mRNA表达均较M组降低（P〈0.05）.结论 水飞蓟素可减轻肾组织损害,延缓肾间质纤维化的进展,可能与其抑制肾组织TSP-1及TGF-β1的表达有关.

Objective To explore the effect of silymarm on tubulointerstitial fibrosis and the possible mechanism. Methods Thirty-six male SD rats were randomly divided into three groups： control group （group C, sham operation）, UUO group （group M） and UUO silymarin-treated group （group S） （6 animals each group）. Half of the rats in each group were sacrificed at the day 7 after operation, so did the rest at the day 21. The pathological changes of the renal tissue were examined by HE, PAS, and Masson stain. Reverse transcription-polymerase chain reaction was applied to detect the mRNA expression of TSP-1 and TGF-β1. Results At the 7th day after operation, tubular expansion, light necrosis of the tubular epithelial cells, interstitial edema, slight interstitial fibrosis and inflammation were observed under a microscope in group M, but the pathological change was more severe in group M than in group S （P〈0. 05）. At the 21st day, in group M, the tubular expansion and necrosis of the epithelial cells were worsened, and the interstitial fibrosis aggravated. The injury of the renal tissue was alleviated in group S as compared with group M （P〈0. 05）. The mRNA expression of TGF-β1 and TSP-1 in renal tissues of group M was increased significantly （P〈0. 01 ） at the 7th and 21st day as comparedwith group C, and that was lower in group S than in group M （P〈0. 05）. Conclusions Silymarin improved the injury of the renal tissue, and retarded the development of tubulo-interstitial fibrosis probably through inhibiting the expression of TSP-1 and TGF-β1.