川陈皮素对非酒精性脂肪性肝病大鼠肝脏脂代谢相关因子蛋白及mRNA表达的影响  

Effect of Nobiletin on Expression and mRNA Level of Hepatic Lipid Metabolism Related Factors in Rat Model of Non-alcoholic Fatty Liver Disease

作　　者：石安华 范英昌[1] 姚政 武俊紫 赵梓铭 王维 陆登成 陈文慧 SHI An-hua;FAN Ying-chang;YAO Zheng;WU Jun-zi;ZHAO Zi-ming;WANG Wei;LU Deng-cheng;CHEN Wen-hui(Tianjin University of Chinese Medicine,Tianjin 300193,China;Yunnan University Of Chinese Medicine,Kunming Yunnan 650500,China)

机构地区：[1]天津中医药大学,天津300193 [2]云南中医药大学,云南昆明650500

出　　处：《中医药导报》2020年第5期39-44,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金地区基金项目(81760818);天津中医药大学中西医结合学院研究生创新基金项目(CXJJLX201715)。

摘　　要：目的:分析川陈皮素对非酒精性脂肪性肝病大鼠肝脏脂代谢相关因子蛋白及mRNA表达的影响,以探讨川陈皮素对非酒精性脂肪性肝病大鼠的保护作用及可能机制。方法:72只SD大鼠适应性喂养2周后,按照随机数字表法分为正常组、模型组、水飞蓟素组以及川陈皮素低、中、高剂量组。采用高脂饲料喂养8周成功复制非酒精性脂肪性肝病大鼠模型后给予相应药物治疗6周,检测大鼠肝脏病理学、肝功能、血脂、氧化和抗氧化指标,同时采用Western Blotting和Real-time PCR法检测肝脏脂代谢相关因子SREBP-1c、CHREBP、ACC、SCD1、PPARα、ACOX1、CPT1A和Cyp4501A1蛋白及mRNA表达水平。结果:光镜下,正常组肝细胞大小均一,模型组可见大量脂肪空泡及炎细胞浸润;水飞蓟素组以及川陈皮素低、中、高剂量组脂肪空泡数量明显低于模型组,但仍有一定的炎细胞浸润;模型组ALT、AST、TG、TC、MDA高于正常组(P<0.05),SOD和GSH低于正常组(P<0.05);模型组SREBP-1c、ACC、Cyp4501A1蛋白及mRNA表达高于正常组(P<0.05),CHREBP、SCD1、PPARα、ACOX1、CPT1A蛋白及mRNA表达低于正常组(P<0.05)。水飞蓟素组以及川陈皮素低、中、高剂量组ALT、AST、TG、TC、MDA低于模型组(P<0.05),SOD和GSH高于模型组(P<0.05);水飞蓟素组以及川陈皮素低、中、高剂量组SREBP-1c、ACC、Cyp4501A1蛋白及mRNA表达低于模型组(P<0.05),CHREBP、SCD1、PPARα、ACOX1、CPT1A蛋白及mRNA表达高于模型组(P<0.05)。结论:川陈皮素对高脂饮食诱导的非酒精性脂肪性肝病大鼠肝脏具有明显的保护作用,其作用机理可能是调节脂肪酸代谢,提高抗氧化能力。Objective:To investigate the effect of nobiletin on protein and mRNA expression of hepatic lipid metabolism-related factors in rats with nonalcoholic fatty liver disease(NAFLD),and to explore the protective effect and possible mechanism of nobiletin on rats with NAFLD.Methods:72 SD rats were randomly divided into control group,model group,silymarin treatment group[14 mg/(kg·d)],and nobiletin treatment groups of low dose[100 mg/(kg·d)],medium dose[200 mg/(kg·d)]and high dose[400 mg/(kg·d)].The NAFLD model was successfully established by 8 weeks of high-fat diet,followed by 6 weeks of treatment.After scarification,the liver pathology,liver function,blood lipid,oxidation and antioxidation indexes were detected.The expression of SREBP-1c,ChREBP,ACC,SCD1,PPARα,acox1,CPT1A and CYP4501A1 protein and mRNA were detected by Western blotting and real time PCR.Results:Under the light microscope,the size of hepatocytes in the normal group was uniform,and a large number of fat vacuoles and inflammatory cell infiltration could be seen in the model group;the number of fat vacuoles in the silymarin group and the low,medium and high doses of kaempferin group was significantly lower than that in the model group,but there was still some inflammatory cell infiltration.In the model group,ALT,AST,TG,TC,MDA were higher than those in the normal group(P<0.05),SOD and GSH were lower than those in the normal group(P<0.05),SREBP-1c,ACC,CYP4501A1 protein and mRNA expression were higher than those in the normal group(P<0.05),ChREBP,SCD1,PPARα,acox1,CPT1A protein and mRNA expression were lower than those in the normal group(P<0.05).ALT,AST,TG,TC and MDA in silymarin group and low,medium and high dosage of nobiletin groups were lower than those in model group(P<0.05),whlie SOD,GSH were higher than those in model group(P<0.05).The expression of SREBP-1c,ACC,Cyp4501A1 protein and mRNA in silymarin group and low,medium and high dosage of nobiletin were lower than that in model group(P<0.05),and the expression of ChREBP,SCD1,PPARα,ACOX1,CPT1A

关 键 词：川陈皮素 非酒精性脂肪性肝病 大鼠 脂代谢相关因子 

分 类 号：R285.5[医药卫生—中药学]