紫铆因改善非酒精性脂肪性肝炎及作用机制研究  

Improvement of non-alcoholic steatohepatitis by Butein and research on its mechanism

作　　者：刘静[1] 侯凯 张丽 LIU Jing;HOU Kai;ZHANG Li(Zhongda Hospital Affiliated to Southeast University,Department of Pharmacy,Nanjing 210009,Jiangsu,China;Westlake Laboratory,Hangzhou 310000,Zhejiang,China)

机构地区：[1]东南大学附属中大医院药学部,江苏南京210009 [2]西湖实验室,浙江杭州310000

出　　处：《中国临床药理学与治疗学》2025年第3期355-365,共11页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：江苏省药学会-正大天晴医院药学科研基金项目(Q202209);江苏省药学会-奥赛康医院药学科研基金项目(A202210)。

摘　　要：目的:研究紫铆因(Butein)对非酒精性脂肪性肝炎(NASH)脂质沉积和炎症反应的调节作用。方法:将HepG2细胞分为溶剂对照组(1‰DMSO)、紫铆因1、3、6、12、25、50μmol/L 6个浓度组,检测细胞存活率,确定紫铆因低、高浓度组。将HepG2细胞分为溶剂对照组(1‰DMSO)、模型组(游离脂肪酸FFA 1 mmol/L体外诱导)、紫铆因低、高浓度组,各组细胞培养24h后,检测甘油三酯(TG),脂质合成相关因子甾醇调节元件-结合蛋白-1c(SREBP-1c)、脂肪酸合酶(FAS)、硬脂酰辅酶A去饱和酶-1(SCD-1),脂质氧化相关因子过氧化物酶体增殖物激活受体-α(PPARα)、肉碱棕榈酰转移酶1A(CPT1A)、丙二酰辅酶A脱羧酶(MLYCD),以及炎症因子肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)的表达水平。应用蛋氨酸胆碱缺乏(MCD)饮食饲养构建NASH小鼠模型,设立正常饮食对照组、模型组、紫铆因低剂量组(100mg·kg^(-1)·d^(-1))、紫铆因高剂量组(200mg·kg^(-1)·d^(-1))。分别喂养4周后,观察各组小鼠肝脏组织的病理变化,检测各组小鼠肝脏、血清TG和总胆固醇(TC)含量,检测肝脏组织内脂质合成相关因子SREBP-1c、FAS、SCD-1和脂质氧化相关因子PPARα、CPT1A、酰基辅酶A氧化酶1(ACOX1)、MLYCD及炎症因子TNF-α、MCP-1蛋白表达水平。结果:与溶剂对照组相比,紫铆因给药浓度≥12μmol/L时对HepG2细胞生长具有抑制作用(P<0.05),设定低、高浓度组分别为5、10μmol/L;与溶剂对照组相比,紫铆因组HepG2细胞内TG含量显著降低(P<0.05);与模型组相比,紫铆因高浓度组细胞内SREBP-1c、FAS、SCD-1的mRNA表达显著降低(P<0.05),而PPARα、CPT1A、MLYCD的mRNA表达显著增高(P<0.05),TNF-α、MCP-1的mRNA表达显著降低(P<0.05)。与模型组相比,紫铆因高浓度组细胞内SREBP-1c、FAS、SCD-1、MCP-1、TNF-α蛋白的表达降低,PPARα、CPT1A、MLYCD蛋白的表达增高。与正常饮食对照组相比,模型组肝组织病理切片表现明AIM:To research the regulatory effects of Butein on lipid deposition and inflammation in non-alcoholic steatohepatitis(NASH).METHODS:HepG2 cells were divided into solvent control group(1‰dimethyl sulfoxide)and different concentration of Butein groups(1,3,6,12,25,50μmol/L).The survival rate of HepG2 cells were detected,the low and high concentration groups of butein were determined.HepG2 cells were divided into solvent control group(1‰DMSO),model group(induction with 1 mmol/L free fatty acids in vitro),low and high concentration of Butein groups.After 24 hours’cell culture in each group,expression of triglyceride(TG),lipid synthesis-related factors SREBP-1c,FAS,SCD-1,lipid oxidation-related factors PPARα,CPT1A,MLYCD,and inflammatory factors TNF-αand MCP-1 in each group were detected.The model of NASH was constructed on C57BL/6J mouse by methionine choline deficiency diet(MCD).Normal diet group(ND group),model group(MCD group),low dose(100 mg·kg^(-1)·d^(-1))and high dose(200 mg·kg^(-1)·d^(-1))of Butein groups were established.After 4 weeks of feeding,pathological changes of liver tissues in each group were observed,contents of liver and serum TG and TC in each group were detected,and protein expression levels of lipid synthesis-related factors SREBP-1c,FAS,SCD-1 and lipid oxidation-related factors PPARα,CPT1A,ACOX1 and MLYCD,inflammatory factors TNF-αand MCP-1in liver tissues were detected.RESULTS:Compared with solvent control group,Butein inhibited HepG2 cell growth when the concentration was≥12μmol/L(P<0.05).Make 5 and 10μmol/L as low and high concentration groups,respectively.Compared with the solvent control group,the intracellular TG content of HepG2 cells in butein group was significantly lower(P<0.05).Compared with the model group,mRNA expressions of SREBP-1c,FAS,and SCD-1 was significantly lower(P<0.05),while mRNA expression of PPARα,CPT1A,and MLYCD was significantly higher(P<0.05),mRNA expression of TNF-α,MCP-1 was significantly decreased(P<0.05)in high-concentration butein group.Compa

关 键 词：紫铆因 非酒精性脂肪性肝炎 脂质沉积 炎症反应 脂质代谢 

分 类 号：R965.2[医药卫生—药理学]