黄芪甲苷对顺铂所致小鼠肝损伤的抑制作用及其机制  

Inhibitory effect of astragalosideⅣon cisplatin-induced liver injury in mice and its mechanism

作　　者：牛凯琦 昌贺 律广富[2] 郑彭予 迟雪婷 周佳 王雨辰 黄晓巍[1,3] NIU Kaiqi;CHANG He;LYU Guangfu;ZHENG Pengyu;CHI Xueting;ZHOU Jia;WANG Yuchen;HUANG Xiaowei(Department of Clinical Pharmacy and Traditional Chinese Medicine Pharmacology,School of Pharmacy,Changchun University of Chinese Medicine,Changchun 130117,China;Pharmacology Group of Chinese Medicine,Jilin Ginseng Research Academy,Changchun University of Chinese Medicine,Changchun 130117,China;Basic Research Institute,Northeast Asia Institute of Traditional Chinese Medicine,Changchun University of Chinese Medicine,Changchun 130117,China)

机构地区：[1]长春中医药大学药学院临床药学与中药药理教研室,吉林长春130117 [2]长春中医药大学吉林省人参研究科学院中药药理组,吉林长春130117 [3]长春中医药大学东北亚中医药研究院基础研究所,吉林长春130117

出　　处：《吉林大学学报(医学版)》2025年第2期370-377,共8页Journal of Jilin University:Medicine Edition

基　　金：吉林省科技厅青年成长科技计划项目(20210508001RQ);吉林省教育厅科学技术一般项目(JJKH20210975KJ)。

摘　　要：目的:探讨黄芪甲苷(AS-Ⅳ)对顺铂(CDDP)所致小鼠肝损伤的抑制作用,并阐明其可能的作用机制。方法:40只体质量为18~22 g的C57BL/6雄性小鼠随机分为对照组、模型组、AS-Ⅳ组和腺苷酸活化蛋白激酶(AMPK)抑制剂(Compound C)+AS-Ⅳ组。对照组和模型组小鼠灌胃等量生理盐水,连续给药9d;AS-Ⅳ组和Compound C+AS-Ⅳ组小鼠灌胃AS-Ⅳ水溶液(150 mg·kg^(-1)·d^(-1));实验第6天Compound C+AS-Ⅳ组小鼠腹腔注射Compound C (20 mg·kg^(-1));第7天除对照组小鼠腹腔注射生理盐水外,其余各组小鼠腹腔注射20 mg·kg^(-1) CDDP建立小鼠肝损伤模型,48 h后处死小鼠。收集各组小鼠血清和肝组织,采用试剂盒检测各组小鼠血清中天冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶(ALT)水平以及肝组织中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性及丙二醛(MDA)水平,HE染色法观察各组小鼠肝组织病理形态学表现,免疫组织化学染色法检测各组小鼠肝组织中谷胱甘肽过氧化物酶4 (GPX4)、铁蛋白重链1 (FTH1)和铁死亡抑制蛋白1 (FSP1)的蛋白表达水平,Western blotting法检测各组小鼠肝组织中核因子E2相关因子2(Nrf2)、血红素氧合酶1 (HO-1)和AMPK蛋白表达水平。结果:与对照组比较,模型组小鼠血清中AST和ALT水平明显升高(P<0.01),肝组织中SOD和CAT活性明显降低(P<0.01),MDA水平明显升高(P<0.01);与模型组比较,AS-Ⅳ组小鼠血清中AST和ALT水平明显降低(P<0.01),肝组织中MDA水平降低(P<0.01),SOD和CAT活性升高(P<0.01);与AS-Ⅳ组比较,Compound C+AS-Ⅳ组小鼠血清中AST和ALT水平升高(P<0.01),肝组织中MDA水平升高(P<0.05),SOD和CAT活性降低(P<0.01)。HE染色,与对照组比较,模型组小鼠肝脏损伤程度增强,肝细胞排列紊乱,部分肝细胞水肿;与模型组比较,AS-Ⅳ组小鼠肝脏形态恢复正常;与AS-Ⅳ组比较,Compound C+AS-Ⅳ组小鼠肝细胞排列紊乱且边缘较为模糊。免疫组织化学法,与对照组比较Objective:To investigate the inhibitory effect of astragalosideⅣ(AS-Ⅳ)on cisplatin(CDDP)-induced liver injury in the mice,and to elucidate its possible mechanism.Methods:Forty male C57BL/6 mice with body weights of 18-22 g were randomly divided into control group,model group,AS-Ⅳgroup and adenosine 5'-monophosphate-activated protein kinase(AMPK)inhibitor(Compound C)+AS-Ⅳgroup.The mice in control group and model group were gavaged with the same volume of normal saline,and the drug was administered continuously for 9 d.The mice in AS-Ⅳgroup and Compound C+AS-Ⅳgroup were given AS-Ⅳaqueous solution(150 mg·kg^(-1)·d^(-1)),respectively.On the 6th day of experiment,the mice in Compound C+AS-Ⅳgroup were intraperitoneally injected with Compound C(20 mg·kg^(-1)),and on the 7th day,except for control group,the mice in other groups were intraperitoneally injected with 20 mg·kg^(-1) CDDP to establish the mouse liver injury models,and the mice were sacrificed 48 h later.Serum and liver tissues were collected,and the levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in the serum of the mice,as well as the activities of superoxide dismutase(SOD)and catalase(CAT)and the levels of malondialdehyde(MDA)in the liver tissue of the mice in various groups were detected by kits.The pathomorphology of liver tissue of the mice in various groups were detected by HE staining.The expression levels of glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1)and ferroptosis inhibitory protein 1(FSP1)proteins in liver tissue of the mice in various groups were detected by immunohistochemical staining,and the expression levels of nuclear factor-E2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and AMPK proteins in liver tissue of the mice in various groups were detected by Western blotting method.Results:Compared with control group,the levels of AST and ALT in serum of the mice in model group were increased(P<0.01),the activities of SOD and CAT in the liver tissue were significantly decreased(P<0.01),and

关 键 词：黄芪甲苷 顺铂 肝损伤 铁死亡 腺苷酸活化蛋白激酶 

分 类 号：R96[医药卫生—药理学]