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茯苓多糖保护对乙酰氨基酚暴露胎鼠的分子机制研究 被引量:12

Molecular mechanism study of Poria Cocos polysaccharides preventing against acetaminophen-exposed fetus mice
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摘要 目的:本文旨在探索茯苓多糖对产前对乙酰氨基酚(APAP)致胎鼠肝损伤的保护作用及分子机制研究。方法:构建产前对乙酰氨基酚(300mg/kg)诱导肝损伤胎鼠(E11.5)模型,随机分成对乙酰氨基酚模型组、N-乙酰半胱氨酸0.1 g/kg组、茯苓多糖0.1、0.2、0.4 g/kg组,持续灌胃7天,同时设正常对照组。末次给药后收集胎鼠肝组织标本,经生化法测定肝组织中谷丙转氨酶(ALT)和谷草转氨酶(AST)含量,酶联免疫吸附(ELISA)法测定肝匀浆中成纤维细胞生长因子21(FGF21)浓度,免疫荧光法检测分析肝脏细胞中FGF21阳性标记细胞计数,以及Western blot印迹法测定肝脏细胞中蛋白激酶B (AKT)及其磷酸化表达的变化情况。结果:与正常胎鼠比较,对乙酰氨基酚胎鼠肝组织ALT、AST含量明显升高,肝匀浆FGF21含量明显下降,肝脏细胞FGF21阳性细胞显著减少,肝细胞内源性蛋白激酶B (AKT)表达水平明显减少。与对乙酰氨基酚胎鼠组比较,茯苓多糖各组胎鼠肝组织中ALT和AST浓度明显降低,肝匀浆中FGF21含量明显升高,肝脏细胞中FGF21荧光标记细胞明显增加,同时肝脏细胞AKT及其磷酸化表型表达水平明显上调。结论:茯苓多糖对产前对乙酰氨基酚暴露所致肝损伤胎鼠具有细胞保护的药理活性,其作用机制与介导肝脏细胞AKT信号通路活化而改善肝细胞功能有关。 Objective:Our study aimed to explore the molecular mechanism of Poria Cocos polysaccharides preventing against prenatal acetaminophen(APAP)-induced liver injury in fetus mice.Methods:Prenatal exposure of acetaminophen(APAP;300 mg/kg)was employed to induce liver damage model in E12.5 mice.Mice were randomly divided into five groups:acetaminophen model group,N-acetylcysteine(0.1 g/kg),three doses of Poria Cocos polysaccharides groups(0.1,0.2,0.4 g/kg)and the control group.Mice were orally administered daily for seven days.At the end of administration,liver tissues were collected to determine the contents of alanine transaminase(ALT)and aspartate transaminase(AST).The level of fibroblast growth factor 21(FGF21)was determined by ELISA.The count of FGF21-labeled cells in liver cells was assayed by immunofluorescence,the expressions of protein kinase B(AKT)and related phosphorylation in liver cells were tested by Western blot.Results:Compared to the control group,the levels of ALT and AST in liver tissues were significantly increased in acetaminophen group,FGF21 level was decreased,the number of FGF21 positive cells in liver cells was significantly decreased,the expression level of endogenous protein kinase B(AKT)in hepatocytes was decreased.Compared to acetaminophen group,the content of ALT and AST in liver tissues was reduced in all doses of Poria Cocos polysaccharides group,FGF21 level was elevated,and FGF21-labeled cells were up-regulated,the expression of AKT and the levels of phosphorylation in liver cells were increased.Conclusion:Poria Cocos polysaccharides has the cytoprotective activity on prenatal acetaminophen-induced liver injury of fetus mice,its mechanisms may be related to improving the hepatocellular functions by activating the AKT signal pathway.
作者 兰量园 吴咖 吴欣谋 杨斌 Lan Liangyuan;Wu Ka;Wu Xinmou;Yang Bin(Liuzhou Workers Hospital,Department of Pharmacy,Liuzhou 545005;The Second People's Hospital of Nanning City,Nanning 530031;Guangxi Medical University,School of Pharmacy,Nanning 530021)
出处 《中药药理与临床》 CAS CSCD 北大核心 2019年第2期52-55,共4页 Pharmacology and Clinics of Chinese Materia Medica
基金 广西自然科学基金项目(2017GXNSFBA198049)
关键词 茯苓多糖 乙酰氨基酚 胎鼠 肝损伤 细胞保护 Poria Cocos polysaccharides acetaminophen fetus liver injury cytoprotection
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