橙皮苷对果糖诱导的非酒精性脂肪肝病小鼠肝脏组织中CYP2E1表达的影响  

Effect of hesperidin on CYP2E1 expression in nonalcoholic fatty liver rats induced by high fructose diet

作　　者：李晓霞 方春华 许莹 徐波 郑小岚 LI Xiaoxia;FANG Chunhua;XU Ying;XU Bo;ZHENG Xiaolan(The Fifth Hospital of Wuhan/The Second Affiliated Hospital of Jianghan University,Wuhan 430050,Hubei,China)

机构地区：[1]武汉市第五医院/江汉大学第二附属医院,湖北武汉430050

出　　处：《现代中西医结合杂志》2020年第24期2635-2639,共5页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：武汉市卫生计生委面上项目(WX17D32)。

摘　　要：目的探讨橙皮苷对果糖+高脂饮食构建的非酒精性脂肪肝病(NAFLD)小鼠的干预作用及作用机制。方法60只雄性昆明小鼠适应性喂养1周后按照随机数字表法分为正常组、模型组、多烯磷脂酰胆碱组、橙皮苷低剂量组、橙皮苷中剂量组和橙皮苷高剂量组各10只。除正常组外,其余组小鼠均采用高脂饲料+10%果糖水日常饮用8周构建NAFLD模型,然后多烯磷脂酰胆碱组给予多烯磷脂酰胆碱23 mg/(kg·d)灌胃,橙皮苷低、中、高剂量组分别给予80 mg/(kg·d)、160 mg/(kg·d)和320 mg/(kg·d)灌胃橙皮苷灌胃。灌胃4周后采血检测各组小鼠肝功能指标[谷草转氨酶(AST)、谷丙转氨酶(ALT)]、血脂指标[高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)]、氧化应激指标[谷胱甘肽(GSH)、超氧化物歧化酶(SOD)],观察各组小鼠肝脏病理学变化,实时荧光定量PCR和Western blot法检测肝脏组织中细胞色素P4502E1(CYP2E1)mRNA和蛋白表达情况。结果与正常组比较,模型组小鼠血清AST、ALT、HDL-C和LDL-C水平均明显升高(P均<0.05),GSH和SOD水平均明显降低(P均<0.05);与模型组比较,各药物组小鼠血清AST、ALT和LDL-C水平均明显降低(P均<0.05),HDL-C水平均无明显变化(P均>0.05),GSH和SOD水平均明显升高(P均<0.05)。模型组小鼠肝脏组织有明显脂肪空泡,而各药物组脂肪空泡数量较少。与正常组比较,模型组小鼠肝脏组织中CYP2E1蛋白及mRNA表达水平均明显升高(P均<0.05);与模型组比较,各药物组小鼠肝脏组织中CYP2E1蛋白及mRNA表达水平均明显降低(P均<0.05),但橙皮苷各剂量组仍明显高于多烯磷脂酰胆碱组(P均<0.05)。结论橙皮苷对NAFLD小鼠有明显治疗作用,其综合疗效与多烯磷脂酰胆碱相似,CYP2E1可能是其作用的一个靶点。Objective It is to observe the intervention effect of hesperidin on the non-alcoholic fatty liver disease(NAFLD)mice constructed by fructose+high-fat diet and research its mechanism.Methods After one week of adaptive feeding,60 Kunming mice were divided into 6 groups via random number method,which were the normal group,model group,polyene phosphatidylcholine group,and low-dose,medium-dose and high-dose group of nobiletin,10 mice in each group.Except for the normal group,the mice in the other groups were fed with high-fat diet+10%fructose water daily for 8 weeks to build NAFLD models,and then the polyene phosphatidylcholine group was given polyene phosphatidylcholine 23 mg/(kg·d)by gavage,low-dose,medium-dose and high-dose groups of nobiletin were given 80 mg/(kg·d),160 mg/(kg·d)and 320 mg/(kg·d)hesperidin by gavage.After 4 weeks of intragastric administration,the blood of the mice in each group was collected to detect liver function indexes[aspartate aminotransferase(AST),alanine aminotransferase(ALT)],blood lipid indexes[high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)],oxidative stress indicators[glutathione(GSH),superoxide dismutase(SOD)],the pathological changes in the liver of the mice in each group were observed,and Real-time fluorescent quantitative PCR and Western blot were used to detect the expression of cytochrome P4502E1(CYP2E1)mRNA and protein in liver tissues.Result Compared with the normal group,the levels of serum AST,ALT,HDL-C,LDL-C of mice in the model group were significantly increased(P<0.05),GSH and SOD were significantly decreased(P<0.05);compared with the model group,the levels of serum AST,ALT,LDL-C of the mice were significantly lower in each treatment group(P<0.05),there was no significant difference in HDL-C,and the levels of GSH and SOD were significantly higher in each treatment group(P<0.05).The liver tissues of mice in the model group had obvious fatty vacuoles,while the number of fatty vacuoles in each treatment group was less.Compared with

关 键 词：非酒精性脂肪肝 橙皮苷 小鼠 细胞色素P4502E1 

分 类 号：R-332[医药卫生]