IL-22介导Notch信号通路促进肝星状细胞凋亡的抗纤维化机制研究  

L-22 mediated Notch signaling pathway promoting apoptosis of hepatic stellate cells

作　　者：王建尧[1] 劳京 郭敬杰 罗玉 王斌[1] WANG Jianyao;LAO Jing;GUO Jingjie;LUO Yu;WANG Bin(Department of General Surgery,Shenzhen Children’s Hospital,Shenzhen,Guangdong 518026,China;Department of General Surgery,Shenzhen Children’s Hospital of China Medical University,Shenzhen,Guangdong 518026,China;Department of General Surgery,Shenzhen Children’s Hospital of Zunyi Medical University,Shenzhen,Guangdong 518026,China)

机构地区：[1]深圳市儿童医院普外科,广东深圳518026 [2]中国医科大学深圳儿童医院普外科,广东深圳518026 [3]遵义医科大学深圳儿童医院普外科,广东深圳518026

出　　处：《中国优生与遗传杂志》2022年第3期417-421,共5页Chinese Journal of Birth Health & Heredity

基　　金：广东省医学科研基金(A2020629);深圳市医疗卫生三名工程项目(SZSM201812055);深圳市医学重点学科建设基金(SZXK035,2020-2024)。

摘　　要：目的 探讨IL-22逆转胆道闭锁肝纤维化的作用及其可能的机制。方法 取人的肝星形细胞系LX-2细胞作为研究对象,检测TGF-β1诱导刺激后Notch3信号通路的表达变化及纤维化相关标志物Collagen I和α-SMA的表达水平。加入外源性IL-22进行干扰,流式细胞术比较干扰前后,Notch3信号通路的表达变化及LX-2细胞的凋亡情况。结果 在TGF-β1诱导的肝纤维化中,Notch3信号通路基因Hes-1、Hes-5以及Notch3的表达增高(P<0.05),肝纤维化指标Collagen和α-SMA的蛋白表达增高(P<0.05)。同时加入外源性的IL-22后,Notch3信号通路基因Hes-1、Hes-5以及Notch3的表达降低(P<0.05),流式细胞术检测同时也显示IL-22可以促进肝星状细胞的凋亡。结论 IL-22可能是通过抑制Notch信号通路,来促进肝星状细胞的凋亡,进而抑制肝纤维化的过程。Objective To investigate the role of IL-22 in reversing hepatic fibrosis in biliary atresia and its possible mechanism.Methods Human hepatic stellate cell line LX-2 was taken as the research object.To detect expression changes of Notch3 signaling pathway and fibrosis related markers collagen I and α-SMA by TGF-β1 induction.Exogenous IL-22 was added for interference.The apoptosis of LX-2 cells before and after interference was compared by flow cytometry,and the expression changes of Notch3 signal pathway were detected.Results In TGF-β1 induction Notch signaling pathway,the expression of Notch 3 signaling pathway genes Hes-1,Hes-5 and Notch3 were increased(P<0.05).The liver fibrosis index of Collagen and α-SMA protein expression were increased(P<0.05).When exogenous IL-22 was added,the expression of Notch3 signaling pathway genes Hes-1,Hes-5 and Notch3 were decreased(P<0.05).Flow cytometry also showed that IL-22could promote the apoptosis of hepatic stellate cells and significantly inhibit hepatic fibrosis.Conclusion IL-22 may promote the apoptosis of hepatic stellate cells and inhibit the process of hepatic fibrosis by inhibiting Notch signaling pathway.

关 键 词：胆道闭锁 IL-22 LX-2 凋亡 

分 类 号：R725.7[医药卫生—儿科]