钙离子/钙调蛋白/钙调蛋白依赖的蛋白激酶Ⅱ信号通路在肝纤维化调控中作用的研究进展  

Advances in regulation of liver fibrosis through ionized free calcium/calmodulin/calmodulin-dependent protein kinaseⅡsignaling pathway

作　　者：刘双飞 张熙冰 焦凌峰 冉江华[1] LIU Shuangfei;ZHANG Xibing;JIAO Lingfeng;RAN Jianghua(Department of Hepatobiliary Pancreatic Vascular Surgery,Ganmei Hospital Affiliated to Kunming Medical University and Kunming First People’s Hospital,Kunming 650034,P.R.China)

机构地区：[1]昆明医科大学附属甘美医院暨昆明市第一人民医院肝胆胰血管外科,昆明650034

出　　处：《中国普外基础与临床杂志》2024年第9期1141-1146,共6页Chinese Journal of Bases and Clinics In General Surgery

基　　金：云南省科技厅科技计划项目-高校联合面上项目(项目编号:2018FH001-074);昆明医科大学研究生创新基金项目(项目编号:2023S115)。

摘　　要：目的总结钙离子(ionized free calcium,Ca^(2+))/钙调蛋白(calmodulin,CaM)/Ca M依赖的蛋白激酶Ⅱ(CaM-dependent protein kinaseⅡ,CaMKⅡ)信号通路在肝纤维化中的作用,为治疗肝纤维化提供理论支撑。对近年来国内外关于Ca^(2+)/CaM/CaMKⅡ信号通路在肝纤维化进程中作用研究的相关文献进行综述。结果Ca^(2+)/CaM/CaMKⅡ信号通路在肝纤维化过程的作用表现为双向调控,可能通过协同血小板源性生长因子或转化生长因子-β1相关途径促进肝星状细胞激活和诱导肝细胞凋亡实现双向调控。结论目前对Ca^(2+)/CaM/CaMKⅡ信号通路在肝纤维化进程中作用研究较少,相关认识仍存不足,未来研究应聚焦于该信号通路在肝纤维化中的作用机制研究,特别是其上游基因或下游靶标蛋白,这将有助于制定出针对性强、效果显著的治疗策略,以期实现肝纤维化甚至肝硬化的逆转,从而为肝纤维化患者提供更有效的治疗选择。Objective To summarize the role of ionized free calcium/calmodulin/calmodulin-dependent protein kinaseⅡ(Ca^(2+)/CaM/CaMKⅡ)signaling pathway in liver fibrosis so as to provide a theoretical basis for the treatment of liver fibrosis.Method The recent literature relevant research on the role of Ca^(2+)/CaM/CaMKⅡsignaling pathway in the process of liver fibrosis both domestically and internationally was reviewed.Results The Ca^(2+)/CaM/CaMKⅡsignaling pathway played a bidirectional regulatory role in the process of liver fibrosis,potentially facilitating the activation of hepatic stellate cells and triggering hepatocyte apoptosis through synergistic transforming growth factor-β1 and plateletderived growth factor pathways.Conclusions At present,there is very little research on the role of Ca^(2+)/CaM/CaMKⅡsignaling pathway in the process of liver fibrosis,and there is still insufficient understanding.Future research should focus on the mechanism of this signaling pathway in liver fibrosis,especially its upstream genes or downstream target proteins,which will aid to develop targeted and effective treatment strategies,achieve the reversal of liver fibrosis and even liver cirrhosis,and provide more effective treatment options for patients with liver fibrosis.

关 键 词：钙离子 钙调蛋白 钙调蛋白依赖激酶Ⅱ 肝纤维化 细胞外基质 

分 类 号：R575.2[医药卫生—消化系统]