化瘀解毒汤对TGF-β_1及MMP_1 mRNA表达作用的探讨

The effect of HuaYu JieDu Tang on TGF-β_1 mRNA and MMP-1 mRNA in renal interstitial fibrosis

目的 :探讨化瘀解毒汤抑制肾间质纤维化的可能作用机制。方法 :采用单侧输尿管梗阻 (UUO)法诱导肾间质纤维化动物模型 ,以免疫组化和原位杂交方法分别检测大鼠肾间质组织ECM成分 (Ⅰ、Ⅲ型胶原 )、TGF -β1mRNA及MMP1mRNA表达 ,并作尿α1-MG检测以及相关肾组织学检查。结果 :模型组和各治疗组大鼠肾组织Ⅰ、Ⅲ型胶原、TGF - β1mRNA的面积比显著增加 (P <0 .0 5 ) ,MMP1mRNA面积比显著降低 (P <0 .0 5 ) ;各治疗组大鼠Ⅰ、Ⅲ型胶原、TGF - β1mRNA面积比较模型组减少 (P <0 .0 5 ) ,MMP1mRNA面积比较模型组增加 (P <0 .0 5 ) ;治疗组中以中药预防组鼠Ⅰ、Ⅲ型胶原、TGF - β1mRNA面积比最低、MMP1mRNA面积比最高 (P <0 .0 5 )。经治疗后肾脏组织病理检查有明显改善。结论 :化瘀解毒汤通过下调TGF - β1mRNA表达、上调MMP1mRNA表达、以抑制肾间质ECM的增生和积聚 ,防止肾间质的纤维化。此外还可减轻肾小管病理性损伤。

Objective: To explore the possible mechanism of HuaYu JieDu Tang in inhibiting renal interstitial fibrosis in rat. Methods: Rat renal interstitial fibrosis model was produced by unilateral ureteral obstruction(UUO). Collagen Ⅰ and collagen Ⅲ of rat renal interstitial tissue were detected by immunohistochemical methods. Transforming growth factor-β 1(TGF-β 1)mRNA and Matrix metalloproteinase 1(MMP-1)mRNA of rat renal interstitial tissue were detected by situ hybridization methods. Urinaryα1-MG was measured and correlated with renal histology. Results: The surface area rate of collagenⅠ, collagen Ⅲ and TGF-β1 mRNA, MMP-1 mRNA of model and all treated rats were obviously higher than that of normal rats (P<0.05). The surface area rate of collagenⅠ and collagen Ⅲ and TGF-β1 mRNA of all treated rats were obviously lower than those of model rats(P<0.05). MMP-1 mRNA expression was higher in treated group than that of model group. The renal histology in all treated rats were better than that of model rats(P<0.05). Conclusion: HuaYu JieDu Tang can inhibit the ccumulation of ECM in renal interstitium and prevent renal interstitial fibrosis by down-regulating TGF-β1 mRNA and up-regulating MMP 1mRNA expression. It also inhibits renal interstitial fibrosis by decreasing renal tubule lesion. -β1 mRNA and up-regulating MMP 1mRNA expression. It also inhibits renal interstitial fibrosis by decreasing renal tubule lesion.