龙胆苦苷对非酒精性脂肪肝病大鼠脂肪酸过氧化酶体β氧化信号通路的影响研究  

Study on the effect of gentiopicroside on fatty acid peroxidase β oxidation signaling pathway in rats with nonalcoholic fatty liver disease

作　　者：武俊紫 杨斌 宋波 姚政 陈文慧 WU Junzi;YANG Bin;SONG Bo;YAO Zheng;CHEN Wenhui(Yunnan University of Traditional Chinese Medicine,Kunming 650504,Yunnan China;Hospital of Yunnan Provincial PAP Corps,Kunming 650111,Yunnan,China)

机构地区：[1]云南中医药大学,云南昆明650504 [2]武警云南省总队医院,云南昆明650111

出　　处：《现代中西医结合杂志》2019年第21期2281-2285,2341,共6页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：国家自然科学基金面上项目(81160492)

摘　　要：目的观察龙胆苦苷对非酒精性脂肪肝病(NAFLD)大鼠的作用,并从过氧化酶体β氧化途径探究其作用机制。方法72只雄性清洁级SD大鼠在适应性喂养10d后按照随机数字法分为正常组、模型组、多烯磷脂酰胆碱组及龙胆苦苷低、中、高剂量组,每组12只。正常组大鼠给予普通饲料饲养,其余5组大鼠给予高脂饲料和5%红糖水饮用饲养,12周后检验造模成功后,正常组、模型组予500μL/(kg·d)生理盐水灌胃,多烯磷脂酰胆碱组予多烯磷脂酰胆碱23mg/(kg·d)灌胃,龙胆苦苷低、中和高剂量组分别予50,100,200mg/(kg·d)龙胆苦苷灌胃,时间均为8周。称体质量,处死大鼠测定肝质量,计算肝质量占体质量百分比;取血检测肝功能[谷草转氨酶(AST)和谷丙转氨酶(ALT)]、血脂[胆固醇(TC)和三酰甘油(TG)];HE染色进行肝脏病理学观察,Westernblot和RT-PCR法检测肝脏组织中乙酰辅酶A氧化酶(ACOX1)和过氧化物酶体增殖物激活受体α(PPARα)蛋白及mRNA表达情况。结果模型组大鼠表现为明显的多饮多食、肥胖和精神倦怠,龙胆苦苷各剂量组上述症状明显较模型组好转。模型组大鼠肝脏切片出现明显脂肪空泡样改变,龙胆苦苷各剂量组脂肪空泡数量明显较模型组减少。模型组大鼠肝质量、体质量、肝质量占体质量百分比及血清AST、ALT、TC、TG水平均明显高于正常组(P均<0.05),多烯磷脂酰胆碱组和龙胆苦苷各剂量组除体质量与模型组相近外,其余指标均明显低于模型组(P均<0.05),且龙胆苦苷高剂量组血清AST、ALT、TC、TG水平均明显低于多烯磷脂酰胆碱组(P均<0.05)。模型组ACOX1和PPARα蛋白及mRNA表达量均明显低于正常组(P均<0.05),多烯磷脂酰胆碱组和龙胆苦苷各剂量组ACOX1和PPARα蛋白及mRNA表达量均明显高于模型组(P均<0.05),且龙胆苦苷各剂量组ACOX1和PPARα蛋白表达量及龙胆苦苷高剂量组ACOX1和PPARαmRNA表达量均明显高于多烯磷脂Objective It is to observe the effect of gentiopicroside (GP) on rats with non-alcoholic fatty liver disease (NAFLD) and explore its mechanism of action from the pathogenesis of peroxidase β oxidation.Methods Seventy-two male clean SD rats were randomly divided into normal group,model group,polyene phosphatidylcholine (PPC) group and low,medium and high dose of GP groups after 10 days of adaptive feeding,12 rats in each group.The rats in the normal group were fed with normal diet,the ones in the other groups were fed with high fat diet plus 5% brown sugar water for 12 weeks to establish NAFLD rat models.After the models were successfully established,the rats in normal group and model group were given 500 μL/(kg·d) normal saline by gavage,the ones were given 23 mg/(kg·d) PPC in PPC group and 50,100,200 mg/(kg·d) GP in the low,medium and high dose groups respectively by gavage.All the rats were treatment for 8 weeks.The body mass was measured,the rats were sacrificed to measure liver mass,and the percentage of liver mass/body mass was calculated;the blood was taken to detect liver function (AST,and ALT),blood lipids (TC,TG);HE staining for liver pathology,Western blot and RT-PCR for detection of acetyl-CoA oxidase (ACOX1) and peroxisome proliferator-activated receptor alpha (PPARα) protein and mRNA expression in liver tissue.Results The rats in the model group showed obvious polydipsia,obesity and mental fatigue,and the above symptoms of every GP group were significantly better than those of the model group.The liver slices of the model group showed obvious vacuolar changes,and the number of fat vacuoles in the every GP group was significantly lower than that of the model group.The liver mass,body mass,percentage of liver mass/body mass and the levels of serum AST,ALT,TC,TG in the model group were significantly higher than those in the normal group( P <0.05),all the indexes above except body mass in PPC group and every GP group were lower than those in the model group( P <0.05),and the serum levels of AST,ALT

关 键 词：龙胆苦苷 非酒精性脂肪肝 乙酰辅酶A氧化酶 过氧化物酶体增殖物激活受体Α 大鼠 

分 类 号：R-332[医药卫生]