6-姜烯酚通过调节AKT/GLUT4信号通路改善老年大鼠脂肪组织胰岛素抵抗作用的研究  

6-Shogaol Improves Insulin Resistance in Adipose Tissue of Aged Rats by Regulating AKT/GLUT4 Pathway

作　　者：李海飞 姚玲[2,3] 袁春琳 赖颖 林雪梅[1] 王建伟[2,3] LI Haifei;YAO Ling;YUAN Chunlin;LAI Ying;LIN Xuemei;WANG Jianwei(College 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;College of Life Sciences,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]重庆医科大学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院,重庆400016

出　　处：《中药新药与临床药理》2019年第5期523-528,共6页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金面上项目(81374033,81673659);重庆市教委课题(KJ1600233);重庆医科大学培育基金(X12100);重庆市科委基础研究与前沿探索一般项目(cstc2018jcyjAX0176)

摘　　要：目的研究6-姜烯酚对老年大鼠脂肪组织胰岛素抵抗的作用及机制。方法将20月龄的SD雄性大鼠随机分为老年对照组、老年6-姜烯酚低剂量组(0.125mg·kg^-1)和高剂量组(0.500mg·kg^-1),取3月龄的SD雄性大鼠为青年对照组。连续灌胃给药7周后,测定血浆葡萄糖、甘油三酯(TG)、胆固醇(TC)、游离脂肪酸(NEFA)和胰岛素的含量,并计算稳态模型胰岛素抵抗指数(HOMA-IR)和脂肪组织胰岛素抵抗指数(Adipo-IR);Western Blot法检测附睾周围脂肪组织(eWAT)总胰岛素受体底物1(IRS-1)、磷酸化IRS-1(丝氨酸307位点)[p-IRS-1(ser307)]、磷脂酰肌醇3-激酶(PI3K)、总蛋白激酶B(AKT)、磷酸化AKT(丝氨酸473位点)[p-AKT(ser473)]、葡萄糖转运蛋白(GLUT)4、eWAT细胞质膜和细胞质GLUT4的表达。结果高剂量的6-姜烯酚显著降低禁食血浆葡萄糖、NEFA和胰岛素的含量,降低HOMA-IR和Adipo-IR(P<0.01,P<0.05),显著升高葡萄糖/胰岛素、NEFA/胰岛素和eWATp-AKT(ser473)/AKT的比值,显著升高eWAT GLUT4、eWAT细胞质膜和细胞质GLUT4的表达(P<0.01,P<0.05)。结论6-姜烯酚能改善衰老相关脂肪组织胰岛素抵抗,其机制可能与上调eWAT p-AKT/AKT的比值和GLUT4的表达有关。Objective To investigate the effects and mechanisms of 6-shogaol on aging-related insulin resistance in rat adipose tissue.Methods Male SD rats(20 months old) were randomized into aged control group,aged low-and high-dose 6-shogaol (0.125 mg·kg^-1,0.500 mg·kg^-1,ig.for 7 weeks) groups.Male SD rats (3 months old)was used as a young control group.Enzymatic method and ELISA were used for the examination of fasting plasma concentrations of glucose,triglyceride(TG),total cholesterol (TC),non-esterified fatty acid (NEFA) and insulin.The expression levels of total insulin receptor substrate-1 (IRS-1),phosphorylated IRS-1 (ser307)[p-IRS-1 (ser307)],phosphatidylinositol 3-kinase(PI3K),total protein kinase B (AKT),phosphorylated AKT (ser473)[p-AKT (ser473)],and glucose transporter-4 (GLUT4) in eWAT of rats were analyzed by Western Blot.Results 6-shogaol (0.500 mg·kg^-1) significantly attenuated higher fasting plasma concentrations of glucose,NEFA,insulin,homeostasis medel of assesment for insulin resistance index (HOMA-IR) and adipose tissue insulin resistance index (Adipo-IR) in aged rats (P < 0.01,P < 0.05).The ratios of glucose to insulin,NEFA to insulin and p-AKT (ser473)/AKT and GLUT4 were significantly increased by 6-shogaol (0.500 mg·kg^-1) treatment in comparison with the aged control group (P < 0.01,P < 0.05).Conclusion 6-shogaol can improve aging-related insulin resistance in eWAT of rats by up-regulating the ratio of p-AKT/AKT and expression of GLUT4.

关 键 词：6-姜烯酚 衰老 磷酸化蛋白激酶B 葡萄糖转运蛋白4 脂肪组织胰岛素抵抗 

分 类 号：R285.5[医药卫生—中药学]