基于外泌体miR-602介导的RASSF1A/p38 MAPK通路对乙肝相关性肝癌术后复发调控机制及健脾化瘀方干预研究

乙肝是我国诱发肝癌的主要因素之一，手术是肝癌的主要治疗手段。本课题基于前期研究，提出外泌体中miR-602表达的变化，可通过抑制RASSF1A基因介导p38 MAPK信号通路的促进乙肝相关性肝癌细胞凋亡，影响肝癌术后休眠/复发。本项目拟先在雄性乙肝病毒转基因小鼠上建立乙肝相关性肝癌术后休眠/复发小鼠模型，探讨外泌体miR-602介导的RASSF1A/p38 MAPK通路对促进乙肝相关性肝癌术后休眠，预防乙肝相关性肝癌术后复发的作用。再运用细胞转染等技术，得到稳定表达RASSF1A、过表达达miR-602的HepG2.2.15细胞，并观察不同状态小鼠脾CTL分别对正常表达和过表达miR-602的肝癌细胞的杀伤活性以及对miR-602介导的RASSF1A/p38 MAPK通路的影响。最终阐明健脾化瘀方预防乙肝相关性肝癌的作用及机制，为中医药干预乙肝相关性肝癌术后复发提供了新的思路。

Hepatitis B is one of the leading causes of liver cancer in China. Surgery is the main treatment of liver cancer. According to our previous researches, we suspected that the expression of miR-602 in exosomes can inhibit the expression of ROSF1A gene, which regulate the p38 MAPK signaling pathway. Then, the miR-602 plays a role in promoting the tumor cells apoptosis and affect the postoperative dormancy/recurrence of liver cancer. We intend to investigate the effect of RTLF1A/p38 MAPK pathway mediated by miR-602 on the postoperative dormancy/ recurrence on HBV-transgenic mice model of hepatitis B-related hepatocellular carcinoma. Then, we observed the cytotoxic activity of spleen CTL in different states to normal expression and overexpression of miR-602 hepatoma cells and the changes of miR-602/RTLF1A/p38 MAPK pathway. Finally, clarify the mechanism of Jianpi Huayu Decoction on the prevention and treatment of hepatitis B-related hepatocellular carcinoma. The results of this research are useful in clinical prevention and treatment of hepatitis B-related hepatocellular carcinoma.