经皮耳穴-迷走神经刺激对糖耐量受损模型大鼠血糖及胰岛素受体表达的影响  

Effect of transcutaneous auricular vagus nerve stimulation on hyperglycemia and insulin receptors expression in impaired glucose tolerance rats

作　　者：张悦 李少源[1] 王俊英[1] 翟煦[2] 张紫璇 荣培晶[1] ZHANG Yue;LI Shao-yuan;WANG Jun-ying;ZHAI Xu;ZHANG Zi-xuan;RONG Pei-jing(Institute of Acupuncture and Moxibustion,China Academy of Chinese Medical Sciences,Beijing 100700,China;Graduate School,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院针灸研究所,北京100700 [2]中国中医科学院研究生院,北京100700

出　　处：《针刺研究》2020年第11期882-887,919,共7页Acupuncture Research

基　　金：国家重点研发计划“中医药现代化研究”重点专项(No.2018YFC1705803);国家自然科学基金面上项目(No.81674072);国家自然科学基金中德合作研究项目(No.GZ1236)。

摘　　要：目的:观察经皮耳穴-迷走神经刺激(taVNS)对糖耐量受损(IGT)模型大鼠血糖调节及下丘脑、肝脏、骨骼肌胰岛素受体(INR)表达的影响,探讨taVNS改善IGT的作用机制。方法:36只雄性Wistar大鼠随机分为正常组、模型组、耳缘-非迷走神经刺激(tnVNS)组、耳穴-迷走神经刺激(taVNS)组,每组9只。正常组予普通饲料喂养,模型组、tnVNS组和taVNS组予高糖高脂饲料喂养联合腹腔注射小剂量链尿佐菌素以制备IGT模型。造模后对tnVNS组和taVNS组大鼠连续干预4周,tnVNS组刺激部位为耳缘区(无迷走神经分布)、taVNS组刺激部位为耳甲区(有迷走神经分布),强度为2 mA,频率为疏密波2 Hz/15 Hz,每次30 min,每天1次,共4周。整个实验持续10周,记录各组大鼠的体质量、空腹血糖(FPG)、餐后2 h血糖(2 h PG),ELISA法,检测血浆胰岛素(INS)、胰高血糖素(GC)、糖化血红蛋白(GHbA1c)水平,Western blot法检测INR在下丘脑、肝脏、骨骼肌中的表达量。结果:造模后与正常组比较,其余3组大鼠体质量均明显增加(P<0.001),FPG和2 h PG升高(P<0.05,P<0.001),符合IGT的诊断标准,提示造模成功。干预后与正常组比较,模型组大鼠体质量明显增加(P<0.001),FPG、2 h PG及GC、GHbA1c含量明显升高(P<0.05,P<0.01),血浆INS含量及下丘脑、肝脏、骨骼肌INR表达明显降低(P<0.001,P<0.01,P<0.05)。干预后与模型组比较,taVNS组大鼠体质量、FPG、2 h PG、血浆GC含量明显降低(P<0.01,P<0.05),INS含量及下丘脑、肝脏、骨骼肌中INR表达明显升高(P<0.001,P<0.01,P<0.05)。干预后与tnVNS组比较,taVNS组大鼠FPG和2 h PG值降低(P<0.05),INS含量及下丘脑、肝脏中INR表达明显升高(P<0.001,P<0.05,P<0.01)。结论:经皮耳穴-迷走神经刺激可调节IGT模型大鼠的FPG和2 h PG,降低GC,提高INS敏感性,上调下丘脑、肝脏、骨骼肌中INR的表达。Objective To explore the effect of transcutaneous auricular vagus nerve stimulation(taVNS)on blood glucose regulation and the expression of insulin receptors(INR)of hypothalamus,liver and skeletal muscle tissues in impaired glucose tolerance(IGT)rats,so as to reveal its mechanisms underlying improvement of IGT.Methods Thirty-six male Wistar rats were randomly divided into control,model,transcutaneous auricular none-vagus nerve stimulation(tnVNS),and taVNS groups(n=9 in each group).The IGT model was established by feeding the rats with high-fat and high-sugar diet for 5 weeks,and subsequent intraperitoneal injection of a dose of streptozotocin(20 mg/kg).Transcutaneous electrostimulation(2 mA,2 Hz/15 Hz)was applied to auricular concha(taVNS)or auricular margin(tnVNS),respectively.The treatment was conducted for 30 min once daily for 4 weeks.The body weight,fasting plasma glucose(FPG),2 h plasma glucose(2 h PG)were recorded every week.The contents of plasma insulin(INS),glucagon(GC),glycosylated hemoglobin(GHbA1 c)were detected by using enzyme linked immunosorbent assay(ELISA).The expression levels of INR in hypothalamus,liver and skeletal muscle tissues were detected by Western blot.Results After modeling,the rats’body weight,the contents of FPG,2 h PG,GC and GHbA1 c were significantly up-regulated(P<0.001,P<0.05,P<0.01),and the content of INS and expression of INR in hypothalamus,liver and skeletal muscle tissues were significantly down-regulated in the model group compared with the control group(P<0.001,P<0.01,P<0.05).Following the treatment,the increased FPG,2 h PG,GC,and the decreased INS and INR expression of hypothalamus,liver and skeletal muscle tissues were apparently reversed in the taVNS group relevant to the model group(P<0.001,P<0.01,P<0.05).Compared with the tnVNS group,the FPG and 2 h PG contents were considerable decreased,and the content of INS and INR expression of hypothalamus and liver were obviously increased in the taVNS group(P<0.001,P<0.05,P<0.01).Conclusion taVNS can improve the blood gluc

关 键 词：经皮耳穴-迷走神经刺激 糖耐量受损 空腹血糖 餐后2 h血糖 胰岛素受体 

分 类 号：R245.9+7[医药卫生—针灸推拿学]