马里苷对酒精性脂肪肝的保护作用及机制  

Protective effect of marein against alcoholic fatty liver and its mechanism

作　　者：牛广豪 徐俊驰[2] 顾利青 许英[1] 顾宇人 宋华峰[2] NIU Guanghao;XU Junchi;GU Liqing;XU Ying;GU Yuren;SONG Huafeng(Clinical Trial Institution Office,the Fifth People’s Hospital of Suzhou(the Affiliated Infectious Diseases Hospital of Soochow University),Jiangsu Suzhou 215000,China;Inspection Center,the Fifth People’s Hospital of Suzhou(the Affiliated Infectious Diseases Hospital of Soochow University),Jiangsu Suzhou 215000,China)

机构地区：[1]苏州市第五人民医院(苏州大学附属传染病医院)临床试验机构办公室,江苏苏州215000 [2]苏州市第五人民医院(苏州大学附属传染病医院)检验中心,江苏苏州215000

出　　处：《中国药房》2024年第9期1044-1049,共6页China Pharmacy

基　　金：国家自然科学基金青年项目(No.81900577);苏州市姑苏卫生人才科研项目(No.GSWS2022089);苏州市科技计划-医工结合协同创新研究项目(No.SLJ2022022)。

摘　　要：目的探究马里苷对酒精性脂肪肝(AFL)的保护作用及可能机制。方法以高度白酒灌胃建立小鼠AFL模型,将小鼠按体重随机分为正常对照组(n=9,0.5%羧甲基纤维素钠溶液)、模型组(n=10,0.5%羧甲基纤维素钠溶液)和马里苷75、150 mg/kg组(n=9);每天灌胃给药1次,连续30 d。末次给药后,测定小鼠肝组织中甘油三酯(TG)、丙二醛(MDA)和超氧化物歧化酶(SOD)水平,观察其肝组织病理形态学变化,测定其肝组织中过氧化物酶体增殖物激活受体α(PPARα)、肉碱棕榈酰转移酶1(CPT-1)和二脂酰甘油酰基转移酶(DGAT)蛋白表达水平。以乙醇诱导结合硫酸亚铁和油酸建立大鼠BRL肝细胞损伤模型,以3、6、12μmol/L马里苷干预24 h,观察肝细胞的脂滴分布,测定细胞中TG、MDA、SOD水平及PPARα、CPT-1、DGAT蛋白表达;经MK886(PPARα抑制剂,10μmol/L)预处理后,将造模肝细胞给予12μmol/L马里苷干预24 h,测定细胞中上述蛋白表达。结果动物实验中,与模型组比较,马里苷75、150 mg/kg组小鼠肝脏脂肪变性程度显著减轻,TG、MDA水平和DGAT蛋白表达水平显著降低(P<0.05或P<0.01),SOD水平及PPARα、CPT-1蛋白水平表达水平显著升高(P<0.05或P<0.01)。细胞实验中,3、6、12μmol/L马里苷作用后可显著减少乙醇诱导肝细胞中脂质堆积,降低细胞中TG、MDA水平和DGAT蛋白表达水平(P<0.05或P<0.01),升高细胞中SOD水平及PPARα、CPT-1蛋白表达水平(P<0.05或P<0.01),且在MK886预处理后马里苷对PPARα、CPT-1和DGAT蛋白表达的影响消失。结论马里苷对AFL具有保护作用,其作用机制可能与抑制氧化应激损伤、改善PPARα介导的脂质代谢信号通路有关。OBJECTIVE To explore the protective effect of marein against alcoholic fatty liver(AFL)and its potential mechanisms.METHODS AFL mice model was established with strong wine by gavage.The mice were randomly divided into normal control group(n=9,0.5%sodium carboxymethyl cellulose solution),model group(n=10,0.5%sodium carboxymethyl cellulose solution)and marein 75 and 150 mg/kg groups(n=9).Mice were given relevant medicine intragastrically,once a day,for consecutive 30 days.After the last medication,the levels of triglyceride(TG),malondialdehyde(MDA),and superoxide dismutase(SOD)in liver tissue were determined,and hepatic histopathological changes of liver tissue were observed;the protein expression levels of peroxisome proliferator-activated receptorα(PPARα),carnitine palmitoyltransferase-1(CPT-1),and diacylglycerol acyltransferase(DGAT)were determined in liver tissue.BRL hepatocytes injury model was induced by ethanol combined with ferrous sulfate and oleic acid;after treatment with 3,6 and 12μmol/L of marein for 24 h,the distribution of lipid droplets,the levels of TG,MDA and SOD and protein expressions of PPARα,CPT-1 and DGAT in hepatocytes were examined.After pretreatment with MK886(PPARαinhibitor,10μmol/L),modeled hepatocytes were treated with 12μmol/L of marein for 24 h,and the protein expressions of PPARα,CPT-1 and DGAT were determined.RESULTS As the results showed in vivo,compared with the model group,after treatment with 75 and 150 mg/kg of marein,the degree of steatosis was significantly reduced,and the levels of TG and MDA and protein expression of DGAT were significantly decreased(P<0.05 or P<0.01);the levels of SOD,protein expressions of PPARαand CPT-1 were significantly increased(P<0.05 or P<0.01).As the results showed in vitro,after treatment with 3,6 and 12μmol/L of marein,the lipid accumulation of hepatocytes was significantly inhibited,and the levels of TG and MDA,protein expression of DGAT were significantly decreased(P<0.05 or P<0.01),while the levels of SOD,protein expressions of PPAR�

关 键 词：马里苷 酒精性脂肪肝 氧化应激 脂质代谢 过氧化物酶体增殖物激活受体Α 

分 类 号：R965[医药卫生—药理学]