基础医学与临床2024，Vol.44Issue(3)：317-324,8.DOI:10.16352/j.issn.1001-6325.2024.03.0317
帕立骨化醇抑制氧化应激减轻小鼠肝细胞紧密连接受损
Paricalcitol inhibition of oxidative stress alleviates the damage of hepatocyte tight junction in mice
摘要
Abstract
Objective To explore the impact of paricalcitol(Pal)on the oxidative stress-induced tight junction dam-age of mouse hepatocytes and its mechanism.Methods A model of cholestatic liver injury was created by routine bile duct ligation.The mice were randomly divided into control group(control),model group(BDL)and treatment group(BDL+Pal).HE staining microscopy was used to observe the morphological changes of liver tissues.The human hepa-toma cell line HepG2 was cultured and divided into blank group,model group(400 μmol/L H2O2)and treatment group(400 μmol/L H2O2+20 nmol/L Pal).Western blot was used to examine the level of tight junction protein 1(ZO-1),occludin,phosphorylated p65(p-p65),phosphorylated ERK(p-ERK)and phosphorylated myosin II regulated light chain(p-MLC)protein were checked in each group.Results Compared with the control group,the level of p-p65,p-ERK and p-MLC in the model group was significantly increased(P＜0.000 1 or P＜0.01 or P＜0.001).The protein expression of ZO-1 and occludin was significantly decreased(P＜0.01).HE staining mi-croscopy showed an increased hepatocyte necrosis and inflammatory cell infiltration.In contrast,the above levels in the treatment group showed an opposite trend relative to the model group.Conclusions Pal is able to alleviate the damage of hepatocyte tight junctions by inhibiting oxidative stress in cholestatic mice and HepG2 cells.Its mecha-nism is potentially related to the inhibition of reactive oxygen species and NF-κB/p65 and ERK signaling pathways.关键词
帕立骨化醇/氧化应激/胆汁淤积/肝损伤Key words
paricalcitol/oxidative stress/cholestasis/liver injury分类
医药卫生引用本文复制引用
张威威,谢婧,李丽华..帕立骨化醇抑制氧化应激减轻小鼠肝细胞紧密连接受损[J].基础医学与临床,2024,44(3):317-324,8.基金项目
浙江省自然科学基金(LY23H030002) （LY23H030002）
