金丝桃苷调控肝脏脂质合成改善小鼠非酒精性脂肪性肝病的机制研究  

Study on the mechanism of hyperoside regulating hepatic lipid synthesis to ameliorate non-alcoholic fatty liver disease in mice

作　　者：龙昌锐 乡世健 张振华 吴辉星[2,3] 周本杰 鲁澄宇 LONG Changrui;XIANG Shijian;ZHANG Zhenhua;WU Huixing;ZHOU Benjie;LU Chengyu(School of Pharmacy,Guangdong Medical University,Guangdong Dongguan 523808,China;Shenzhen Key Laboratory of Active Substances Screening and Transformation of Traditional Chinese Medicine,Guangdong Shenzhen 518107,China;Dept.of Pharmacy,the Seventh Affiliated Hospital of Sun Yat-sen University,Guangdong Shenzhen 518107,China)

机构地区：[1]广东医科大学药学院,广东东莞523808 [2]深圳市中药活性物质筛选与转化重点实验室,广东深圳518107 [3]中山大学附属第七医院药学部,广东深圳518107

出　　处：《中国药房》2025年第6期668-673,共6页China Pharmacy

基　　金：国家自然科学基金项目(No.82074078);广东省基础与应用基础研究基金项目(No.2022A1515220027);深圳市科技计划项目(No.ZDSYS20220606100801003)。

摘　　要：目的研究金丝桃苷(HYP)对非酒精性脂肪性肝病(NAFLD)的改善作用机制。方法将雄性C57BL/6小鼠随机分为正常(NFD)组、模型(HFD)组、HYP组,每组8只。除NFD组外,其余组小鼠喂养HF60高脂饲料诱导NAFLD模型,同时HYP组小鼠每日灌胃100 mg/kg的HYP,持续16周。末次给药16 h后,记录各组小鼠体重、肝脏质量,观察肝脏病理形态学变化及脂质堆积情况,检测肝脏中甘油三酯(TAG)含量和血清中TAG、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)含量;采用液相色谱-串联质谱(LC-MS/MS)法检测小鼠肝脏的脂质变化,进行脂质组学分析,并检测脂质合成相关蛋白过氧化物酶体增殖物激活受体α(PPARα)蛋白的表达情况。将人源肝癌细胞株HepG2分为正常对照组、模型组、HYP低浓度(50μmol/L)组、HYP高浓度(100μmol/L)组、HYP低浓度+GW6471(PPARα抑制剂)组和HYP高浓度+GW6471组,除正常对照组外,其余细胞采用油酸、棕榈酸诱导构建高脂细胞模型,观察各组细胞脂滴蓄积情况,检测其中的TAG含量。结果与HFD组比较,HYP组小鼠肝脏脂肪空泡、脂质堆积、肝脏质量和TAG含量,以及血清中ALT、AST、TAG含量均明显减少,肝组织中PPARα蛋白表达水平显著升高(P<0.05);NAFLD病理形态学变化均有所缓解。脂质组学分析发现HYP能降低肝脏中TAG、二酰甘油等脂质代谢物的相对水平。与模型组比较,HYP低、高浓度组细胞中脂滴蓄积和TAG含量均明显减少,GW6471能显著逆转HYP对上述指标的改善作用(P<0.05)。结论HYP可有效改善高脂饲料诱导的小鼠NAFLD,其机制可能与激活PPARα从而调控肝脏脂质合成有关。OBJECTIVE To investigate the improvement mechanism of hyperoside(HYP)on non-alcoholic fatty liver disease(NAFLD).METHODS Male C57BL/6 mice were randomly divided into normal(NFD)group,model(HFD)group and HYP group,with 8 mice in each group.Except for NFD group,the mice in other groups were fed with HF60 high-fat diet to establish NAFLD model;HYP group was simultaneously given HYP 100 mg/kg intragastrically every day,for 16 consecutive weeks.The body weight and liver weight of mice in each group were recorded 16 h after the last medication;the histopathological changes and lipid accumulation in the liver were observed,and the contents of triglyceride(TAG)in liver tissue and serum contents of TAG,aspartate transaminase(AST)and alanine transaminase(ALT)were measured;LC-MS/MS method was adopted to detect lipid changes in the liver tissue of mice for lipidomics analysis,and protein expressions of lipid synthesis-associated proteins peroxisome proliferator-activated receptorα(PPARα)were also tested.Human hepatocellular carcinoma cell line HepG2 was divided into normal control group,model group,HYP low-concentration group(50μmol/L),HYP high-concentration group(100μmol/L),HYP low-concentration+GW6471(PPARαinhibitor)group,and HYP high-concentration+GW6471 group.Except for normal control group,the remaining cells were induced with oleic acid and palmitic acid to establish a high-fat cell model.The accumulation of lipid droplets in each group of cells was observed,and the TAG content was detected.RESULTS Compared with HFD group,HYP group exhibited significant reductions in liver fat vacuoles,lipid accumulation,liver weight,and TAG content in liver tissue,as well as serum contents of ALT,AST and TAG(P<0.05).Additionally,the expression of PPARαprotein in liver tissue was significantly increased(P<0.05),and the pathological morphological changes associated with NAFLD were alleviated.Lipidomic analysis revealed that HYP significantly reduced the levels of TAG,diacylglycerol and other lipids in the liver.Compared with model

关 键 词：金丝桃苷 非酒精性脂肪性肝病 脂质合成 脂质组学 PPARΑ 

分 类 号：R965[医药卫生—药理学] R575[医药卫生—药学]