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肝纤维化是机体对各种病因所致的慢性肝脏损伤后的一种修复反应,是多种原因引起的慢性肝病向肝硬化发展所共有的病理改变和必经途径。深入探究肝纤维化过程中的细胞和分子机制,寻找新的发病机制和治疗靶点将有助于肝纤维化的诊断和治疗,阻止肝纤维化向肝硬化及肝衰竭发展。微小RNA(microRNA,miRNA)是一类大小为19~22个核苷酸的内源性非编码单链小分子RNA,它是转录后调控基因表达水平的重要机制。既往对miRNA在肝纤维化发病机制和治疗中的研究相对较少,而对于miRNA-10a在肝纤维化中的作用还是一片空白。本研究发现在小鼠肝纤维化的发展过程中伴随着肝组织中miRNA-10a的表达增高(P<0.05),提示miRNA-10a在肝纤维化和肝硬化的发生发展过程中起着重要的调控作用。肝星状细胞活化伴随着miRNA-10a表达的上升(P<0.05),其中肝纤维化的关键细胞因子TGF-β可以诱导肝星状细胞表达miRNA-10a。更重要的是,相对于正常人体肝脏组织,硬化肝组织中miRNA-10a的水平有显著上调(P<0.05)。进一步的研究有望揭示miRNA-10a调控肝纤维化的病理生理机制以及评估其作为诊断和治疗靶点的地位。
Liver fibrosis is a repair reaction of chronic liver damage caused by various causes. It is a common pathological change and necessary pathway for the development of liver cirrhosis caused by various causes. Exploring the cellular and molecular mechanisms in liver fibrosis, looking for new pathogenesis and treatment targets will help diagnose and treat liver fibrosis and prevent the development of hepatic fibrosis to liver cirrhosis and liver failure. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs ranging in size from 19 to 22 nucleotides in size and are important mechanisms for post-transcriptional regulation of gene expression. Previous studies of miRNAs in the pathogenesis and treatment of liver fibrosis are relatively few, while the role of miRNA-10a in liver fibrosis is still a blank. This study found that the expression of miRNA-10a in liver tissues was increased during the development of hepatic fibrosis in mice (P <0.05), suggesting that miRNA-10a plays an important role in the development of hepatic fibrosis and cirrhosis Regulation. Activation of hepatic stellate cells was associated with an increase in miRNA-10a expression (P <0.05). TGF-β, a key cytokine in hepatic fibrosis, induces the expression of miRNA-10a in hepatic stellate cells. More importantly, miRNA-10a levels were significantly up-regulated in cirrhotic liver relative to normal human liver tissue (P <0.05). Further studies are expected to reveal the pathophysiological mechanism of miRNA-10a in regulating hepatic fibrosis and evaluating its role as a diagnostic and therapeutic target.