微小非编码RNA-155对大鼠肝纤维化的影响及其可能性机制

Effect of microRNA-155 on hepatic fibrosis in rats and its mechanism

目的:研究微小RNA(microRNA,miRNA)-155及其靶向蛋白基质金属蛋白酶-9(matrix metalloprotein-9,MMP-9)对大鼠肝纤维化的影响。方法:健康SD大鼠鞘内注射miRNA-155建立大鼠肝纤维化损伤模型,并通ELISA试剂盒检测大鼠血清中Ⅳ型胶原(COL-Ⅳ)的表达变化。应用Wnt/β-Catenin通路抑制剂XAV-939研究Wnt/β-Catenin通路在大鼠肝纤维化中的作用,通过qPCR和Western blot法分别检测肝脏组织中MMP-9 mRNA和蛋白的表达变化。结果:鞘内注射miRNA-1554周后,可观察到血清COL-Ⅳ含量显著增加,而腹腔注射XAV-939抑制剂组大鼠COL-Ⅳ未明显变化。qPCR和Western blot结果显示,肝脏组织中MMP-9 mRNA和蛋白的表达均明显上调。结论:鞘内注射miRNA-155可能通过介导MMP-9表达上调导致大鼠肝纤维化损伤,Wnt/β-Catenin通路可参与miRNA-155所致肝纤维化损伤过程。

Objective To study the effect of microRNA(miRNA)-155 and its target protein matrix metalloprotein-9(MMP-9)on hepatic fibrosis in rats.Methods The model of hepatic fibrosis was established by intrathecal injection of miRNA-155 to SD rat,and the expression of typeⅣcollagen(COL-Ⅳ)in rat serum was detected by ELISA kit.Wnt/β-Catenin pathway inhibitor XAV-939 was used to study the role of Wnt/β-Catenin pathway in hepatic fibrosis of rats,and the expression of MMP-9 mRNA and protein in hepatic fibrosis were detected by qPCR and Western blot,respectively.Results After intrathecal injection of miRNA-155 for 4 weeks,the levels of COL-Ⅳin serum were significantly increased,while the COL-Ⅳin rats with intraperitoneal injection of XAV-939 was not significantly changed.The results of qPCR and Western blot showed that the expression of MMP-9 mRNA and protein in liver tissue were significantly up-regulated,respectively.Conclusion The expression of MMP-9 was up-regulation induced by intrathecal injection of miRNA-155 in hepatic fibrosis of rats,and Wnt/β-Catenin pathway may be involved in the process of hepatic fibrosis induced by miRNA-155.