水飞蓟素缓解四氯化碳所致小鼠急性肝损伤的机制  

Silymarin alleviates acute liver injury in mice induced by carbon tetrachloride

作　　者：张永州 吴先闯 刘瑜新 娄婷婷 陈海洋 ZHANG Yongzhou;WU Xianchuang;LIU Yuxin;LOU Tingting;CHEN Haiyang(Department of Pharmacy,Huaihe Hospital of He nan University,Kaifeng 475000,China)

机构地区：[1]河南大学淮河医院药学部,开封475000

出　　处：《西北药学杂志》2023年第2期64-68,共5页Northwest Pharmaceutical Journal

基　　金：河南省医学科技攻关计划项目(编号:LHGJ20190640)。

摘　　要：目的 探讨水飞蓟素(SM)通过沉默信号调节器1(SIRT1)/叉头转录因子1(FOXO1)通路对四氯化碳(CCl4)所致小鼠急性肝损伤(ALD)和脂质代谢异常的影响。方法 60只雄性小鼠随机均分为对照组、模型组、SM低、SM中和SM高剂量组。SM低、SM中和SM高剂量组灌胃给予SM溶液,末次给药后制备ALD小鼠模型。测定三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)水平;测定丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)的活性;ELISA法测定丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)和超氧化物岐化酶(SOD)的水平;HE染色观察肝组织病理学变化;RT-PCR和Western blot检测SIRT1、FOXO1 mRNA和蛋白表达情况。结果 与模型组比较,SM低、SM中和SM高剂量组小鼠血清TG、TC、LDL-C、ALT、AST和肝组织MDA水平降低,HDL-C、GSH-Px、SOD、SIRT1、FOXO1 mRNA和蛋白水平升高(P<0.05)。结论 水飞蓟素可降低ALD小鼠血脂水平,提高抗氧化能力,在一定程度上修复肝功能,可能与激活SIRT1/FOXO1信号通路有关。Objective To investigate the effects of silymarin(SM) on acute liver injury(ALD) and abnormal lipid metabolism in mice induced by carbon tetrachloride(CCl4) through silencing signal regulator 1(SIRT1)/forkhead transcription factor 1(FOXO1) pathway.Methods 60 male mice were randomly divided into control group, model group, low, medium and high dose SM groups. The low, medium and high dose groups were given SM solution by gavage, and ALD mouse model was prepared after the last administration. The levels of high density lipoprotein cholesterol(HDL-C), triglyceride(TG), total cholesterol(TC) and low density lipoprotein cholesterol(LDL-C) were determined. The activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were measured. The levels of malondialdehyde(MDA), glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD) were measured. The histopathological changes of liver were observed by HE staining. The mRNA and protein expressions of SIRT1 and FOXO1 were detected by RT qPCR and Western blot.Results Compared with the model group, the levels of serum TG, TC, LDL-C, ALT, AST and MDA were decreased, and the levels of HDL-C, GSH-Px, SOD, SIRT1, FOXO1 mRNA and protein expression were increased in low, medium and high dose groups(P<0.05).Conclusion Silymarin can reduce the blood lipid level, improve the antioxidant capacity, repair the liver function of ALD mice to a certain extent and play a liver protective role, which may be related to the activation of SIRT1/FOXO1 signal pathway.

关 键 词：水飞蓟素 急性肝损伤 脂质代谢 四氯化碳 沉默信号调节器1 叉头转录因子1 

分 类 号：R965[医药卫生—药理学]