大黄素甲醚-8-O-β-D-葡萄糖苷通过PI3K/AKT/NF-κB通路干预小鼠急性化学性肝损伤  

Intervention of physcion-8-O-β-D-monoglucoside on acute liver injury induced by CCl_(4) in mice by regulating PI3K/AKT/NF-κB

作　　者：陈亚萍 陈婷 刘玉凤 高小芳 黄黎娜 黄枚[1] 张俊平 陈燕[1] 南丽红[1] CHEN Ya-ping;CHEN Ting;LIU Yu-feng;GAO Xiao-fang;HUANG Li-na;HUANG Mei;ZHANG Jun-ping;CHEN Yan;NAN Li-hong(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Fuzhou Hospital of Traditional Chinese Medicine,Fuzhou 350001,China)

机构地区：[1]福建中医药大学药学院,福建福州350122 [2]福州市中医院,福建福州350001

出　　处：《中国药理学通报》2023年第7期1289-1295,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No.81670543);福建省教育厅中青年教师教育科研项目(科技类)(No.JAT190237)。

摘　　要：目的研究大黄素甲醚-8-O-β-D-葡萄糖苷(physcion-8-O-β-D-monoglucoside,PMG)通过PI3K/AKT/NF-κB信号通路干预四氯化碳(carbon tetrachloride,CCl_(4))急性肝损伤模型小鼠的保肝机制。方法将小鼠随机分为正常对照组、模型组、PMG低、中、高(10、20、40 mg·kg^(-1))剂量组及联苯双酯(300 mg·kg^(-1))阳性对照组。PMG组和联苯双酯组灌胃对应药物混悬液,2次/天,连续3 d,正常对照组和模型组灌胃空白溶剂0.5%羧甲基纤维素钠(CMC-Na)。末次给药1 h后,腹腔注射0.5%CCl_(4)油溶液建立急性肝损伤模型,造模16 h后取材。给药体积均为0.1 mL/10 g体质量。HE染色法评价PMG对肝组织病理变化的改善作用;Hoechst 33342染色法检测肝细胞凋亡数;Western blot法检测肝组织中caspase-3、PI3K、p-PI3K、AKT、p-Akt、IκB、p-IκB总蛋白及NF-κB p65核蛋白表达水平;流式细胞术检测小鼠肝组织中辅助性T细胞17(T helper cell 17,Th17)的细胞比例。结果PMG干预可改善肝组织病理损伤程度,能明显抑制肝细胞凋亡,降低caspase-3蛋白表达水平,并能明显降低NF-κB p65核蛋白表达水平,以及PI3K、AKT、IκB蛋白磷酸化水平,降低肝组织中Th17细胞比例。结论PMG可抑制CCl_(4)致小鼠肝细胞凋亡,抑制肝脏过度炎症反应,其作用可能与其影响PI3K/AKT信号通路调控NF-κB激活有关。Aim To investigate the effect of PI3K/AKT/NF-κB signaling pathway in the treatment of physcion-8-O-β-D-monoglu-coside(PMG)on acute liver injury induced by carbon tetracloride(CCl_(4))in mice.Methods Mice were randomly assigned into control group,model group,PMG low-dose,medium-dose and high-dose groups and Bifendate groups.After the continuous intervention with PMG for three days,CCl_(4) oil solution was intraperitoneally injected to establish acute liver injury mouse models,and samples were collected sixteen hours later.HE staining was used to observe the pathological changes of liver tissue.Hoechst 33342 staining was used to detect the number of apoptotic hepatocytes.Western blot was employed to detect the expression levels of caspase-3,PI3K,p-PI3K,AKT,p-Akt,IκB,p-IκB total protein and the nuclear protein NF-κB p65 in mouse liver tissue.The proportion of Th17 cells in mouse liver tissue was detected by FACS.Results After three days of PMG treatment,the pathological injury of liver tissue was relieved,the apoptosis of liver cells and the protein levels of caspase-3(P<0.01)were alleviated compared with model group.PMG could significantly decrease the nuclear expression of NF-κB p65 in the liver of mice with acute liver injury(P<0.05 or P<0.01).The phosphorylation levels of PI3K,AKT and IκB significantly decreased by PMG(P<0.05 or P<0.01).Otherwise,the proportion of Th17 cells in liver tissue was significantly reduced after PMG treatment(P<0.01).Conclusion PMG can alleviate CCl_(4)-induced acute liver injury through PI3K/AKT/NF-κB signaling pathway.

关 键 词：大黄素甲醚-8-O-β-D-葡萄糖苷 急性化学性肝损伤 凋亡 炎症 NF-ΚB激活 PI3K/AKT信号通路 

分 类 号：R-332[医药卫生] R285.5R322.47R329.25R364.5R575