中文摘要
肝纤维化是肝硬化、肝癌等的前期病理学改变阶段。肝纤维化是一种针对急性或慢性肝细胞损伤的可逆性的愈合反应,反映了肝脏修复与疤痕形成之间的平衡状态。因此,在肝脏疾病治疗领域,大量的研究针对于肝纤维化可逆性愈合的分子机制,以期发现新的基因分子治疗靶点,达到肝组织修复愈合的目的。肝刺激因子(hepatic stimulatorsubstance,HSS)是一种肝脏特异性促生长因子,已有实验证明HSS可有效促进肝细胞增殖。然而,HSS应用于肝纤维化治疗中仍有问题待解决。miR-483是一类在肝脏内发现并鉴定的小分子非编码RNA,由类胰岛素生长因子2(insulin growth factor 2,IGF2)基因第二内含子编码生成。已有文献证明miR-483所在的宿主基因IGF2在发育、细胞再生修复等过程中发挥重要功能。本项目组前期研究发现miR-483可在体内和体外实验中有效抑制肝纤维化。综上所述,本项目组与俄罗斯谢切诺夫莫斯科国立医科大学肝胆胰再生外科研究中心合作,探讨miR-483在HSS介导的肝纤维化逆转愈合中的作用,将对有效发挥HSS促进肝纤维化的治疗,具有重要临床意义和社会价值。
英文摘要
Liver fibrosis a pathological changes of the early stage during a large number of serious liver disease such as cirrhosis, liver cancer and others, it is a healing response to acute or chronic irreversible liver cell damage, which reflect the equilibrium between reversible liver healing repair and scar formation. Therefore, in the therapeutic areas of liver disease, a lot of research focus on the molecular mechanism of liver fibrosis reversible healing, in order to discover new genetic and molecular therapeutic targets and effectively promote the course of liver fibrosis reversal, getting the liver tissue healing purpose. Hepatic stimulator substance(HSS) is a liver-specific growth factors, in vivo and in vitro experiments have proved that HSS can effectively promote hepatocyte proliferation. However, the HSS used in the treatment of liver fibrosis, there are still some issues to be resolved. miR-483 is found and identified as a class of small molecules in the liver of non-coding RNA, the insulin growth factor 2 (IGF2) gene intron code generation. MiR-483 have been documented where the host gene IGF2 play a vital role in development, cell regeneration and repair process. The project team preliminary study found that miR-483 can effectively inhibit liver fibrosis in vivo and in vitro experiments. In summary, the project group and Russian Sechenov Moscow State Medical University, Hepatobiliary and Pancreatic Regeneration Surgery Research Center, to explore role of miR-483 in reversing healing during the HSS mediated liver fibrosis, will effectively promote the HSS treatment of liver fibrosis, and make important clinical significance and social value.
结题摘要
肝纤维化是一种针对急性或慢性肝细胞损伤的可逆性的愈合反应,这种可逆性的愈合反映了肝脏修复与疤痕形成之间的平衡状态。因此,在肝脏疾病治疗领域,大量的研究针对于肝纤维化可逆性愈合的分子机制,以期发现新的基因分子治疗靶点,有效地促进肝纤维化病程中的逆转,达到肝组织修复愈合的目的。本项目组与俄罗斯谢切诺夫莫斯科国立医科大学肝胆胰再生外科研究中心合作,阐明miR-483在肝刺激因子(hepatic stimulator substance, HSS)介导的肝纤维化逆转愈合中的功能及作用机制,将对有效发挥HSS促增殖功能、减少HSS相关毒副作用、促进肝纤维化的治疗以及发现联合治疗中新的药物靶点具有深远的临床意义和社会价值。本项目合作交流期间,中俄双方研究人员对miR-483在HSS介导的肝纤维化逆转愈合中的作用研究进行了合作交流方案的探讨与制定,并签订了相关协议。同时,中方研究人员就项目合作过程中涉及到的肝脏细胞间通过微囊泡传递非编码RNA这一内容进行了相关研究并取得了初步成果。微囊泡排放机制的研究将有效促进肝纤维化逆转过程中非编码RNA传递的作用与机制的研究。
