生姜提取物调节骨骼肌CD36和PPARα改善高果糖饮食大鼠胰岛素敏感性  

Improvement of Liquid Fructose-induced Skeletal Muscle Insulin Sensitivity in Rats by Ginger Treatment Is Associated with CD36 and PPARα

作　　者：张军[1,2] 曾颜 靳雅倩 王同壮 席雨蒙 王猛 姚玲 李春莉 柯大智[5] 林雪梅[1] 王建伟[2,3] ZHANG Jun;ZENG Yan;JIN Yaqian;WANG Tongzhuang;XI Yumeng;WANG Meng;YAO Ling;LI Chunli;KE Dazhi;LIN Xuemei;WANG Jianwei(Faculty of Basic Medical Sciences,Chongqing Medical University,Chongqing 400016,China;Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases,Chongqing Medical University,Chongqing 400016,China;College of Traditional Chinese Medicine,Chongqing Medical University,Chongqing 400016,China;Faculty of Life Sciences,Chongqing Medical University,Chongqing 400016,China;The Second Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]重庆医科大学基础医学院,重庆400016 [2]中医药防治代谢性疾病重庆市重点实验室,重庆400016 [3]重庆医科大学中医药学院,重庆400016 [4]重庆医科大学生命科学研究院,重庆400016 [5]重庆医科大学第二附属医院,重庆400016

出　　处：《中药新药与临床药理》2020年第6期621-626,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金面上项目(81973653,81673659,81374033);重庆市科委基础研究与前沿探索一般项目(cstc2018jcyjAX0176,cstc2017jcyjAX0374);重庆市卫生健康委员会中医药科技项目(ZY201702133)。

摘　　要：目的观察生姜提取物对高果糖饮食大鼠骨骼肌胰岛素敏感性的影响,并探讨其可能的作用机制。方法取SD大鼠24只,随机分为4组,每组6只,即正常对照组,模型组,生姜提取物低、高剂量组(20、50 mg·kg^-1),模型复制的同时连续给药28 d;取血检测各生化指标并计算胰岛素敏感性指数(ISI)、胰岛素抵抗指数(HOMA-IR),检测游离脂肪酸(NEFA/FFA)含量;RT-PCR和Western Blot法检测骨骼肌中相关基因和蛋白的表达。结果生姜提取物逆转了高果糖饮食引起的ISI的降低与HOMA-IR的升高(P <0.05),降低了血浆NEFA的含量(P <0.05);明显提高果糖饮食大鼠骨骼肌过氧化物酶体增殖物激活受体(PPAR)α mRNA的表达(P <0.01),但对磷脂酰肌醇3-激酶(PI3K)、胰岛素受体底物1(IRS-1)、蛋白激酶B(Akt)、脂肪酸转位酶(FAT/CD36)、葡萄糖转运蛋白(GLUT)4、过氧化物酶体增殖物活化受体γ协同激活因子(PGC)1α和肉毒碱棕榈酰转移酶(CPT)1β mRNA的表达并无明显影响;提高了骨骼肌磷酸化蛋白激酶B(p-Akt)对总蛋白激酶B(Akt)蛋白表达的的比值(P <0.05),增强了骨骼肌CD36和PPARα的蛋白表达(P <0.05)。结论生姜提取物能够改善高果糖饮食大鼠骨骼肌胰岛素敏感性,其机制可能与提高p-Akt/Akt蛋白表达比值、CD36蛋白表达以及PPARα的基因与蛋白表达有关。Objective To investigate the effects and mechanism of ginger on liquid fructose-induced skeletal muscle insulin sensitivity in rats. Methods Twenty four male SD rats were randomized into normal group,model group,low and high doses of alcoholic extract of ginger treatment groups(20 mg·kg^-1),50 mg·kg^-1,ig.). Rat models of skeletal muscle insulin sensitivity were induced by feeding with liquid fructose for 4 weeks,and the drugs were continuously given during the same period of modelling. The blood samples were taken from rats to detect biochemical indexes,non-esterified fatty acid(NEFA/FFA),and calculate insulin sensitivity index(ISI),homeostasis model assessment of insulin sensitivity(HOMA-IR). RT-PCR and Western Blot were used to detect the expression of m RNA and proteins in skeletal muscle. Results Ginger treatment reversed the liquid fructose-induced low ISI and high HOMA-IR,decreased NEFA(P < 0.05),increased the PPARα m RNA expression(P < 0.01);but had no significant effect on the expression of PI3K, IRS-1, Akt, CD36, GLUT4, PGC1α and CPT1β;furthermore, it improved the protein expression of CD36,PPARα and the ratio of p-Akt/Akt in skeletal muscle of rats(P < 0.05). Conclusion Alcoholic extract of ginger can improve fructose-induced skeletal muscle insulin sensitivity by up-regulating the p-Akt/Akt,CD36 and PPARα protein,as well as the PPARα mRNA.

关 键 词：生姜提取物 胰岛素敏感性 CD36 PPARΑ 果糖 骨骼肌 大鼠 

分 类 号：R285.5[医药卫生—中药学]