耳甲电针调节糖耐量减低机制研究

Impaired Glucose Tolerance (IGT) is an abnormal metabolic state following glucose metabolic steady state but prior to diabetes. IGT is an important stage during the progression of diabetes, with an underlying mechanism of insulin resistance and pancreatic β cell dysfunction. IGT is one of the diseases that shows significant beneficial response to acupuncture treatment. Original findings from our laboratory show that transcutaneous auricular vagus nerve stimulation (taVNS) which is innervated by vagus nerve, would enhance the activity of pancreatic β cells, promote the secretion of insulin, upregulate the expression of insulin receptors in central as well as peripheral tissues, thus to improve glycometabolism. In this study, we would further illuminate the mechanism of taVNS at “yidan-pi” auricular acupoints on the regulation of glucose metabolism, its improvement of the IGT state in rat model, as well as its regulation effect on insulin receptor expression and insulin resistance, and systematically illustrate the clinical effective of this treatment on IGT, with emphasize on its influence on the concentrations of glucose and HbA1c, and thus provide an effective proposal for clinical acupuncture.

糖耐量减低（Impaired Glucose Tolerance, IGT）是一种处于正常葡萄糖稳态和糖尿病之间的异常代谢状态，是糖尿病病程中的一个重要阶段，发生机制主要是胰岛素抵抗和胰岛β细胞功能减低。IGT是针灸治疗的适宜病种。我们前期的工作证明耳甲区有迷走神经末梢分布，经皮耳甲迷走神经刺激（transcutaneous auricular vagus nerve stimulation，taVNS）能够提高迷走神经系统的兴奋状态，增强胰岛β-细胞活性，促进胰岛素的分泌，上调中枢和外周组织胰岛素受体的表达，改善糖代谢。本研究目的：1）通过动物实验进一步阐明耳甲（“胰胆-脾”穴）电针调节IGT模型大鼠糖代谢、改善IGT状态，及其对胰岛素受体表达和胰岛素抵抗的作用机制；2）系统观察该疗法对IGT和空腹血糖受损患者的血糖水平和糖化血红蛋白浓度的影响，为临床提供有效的治疗方案。

糖耐量受损(Impaired Glucose Tolerance, IGT)是介于正常与糖尿病之间的一种中间状态，属于糖尿病前期，诊断指标为空腹血糖(Fasting Plasma Glucose, FPG)＜7mmol/L且餐后2h血糖(2h Plasma Glucose, 2hPG)在7.8mmol/L-11.1mmol/L之间，其发病机制与遗传、胰岛素抵抗、胰岛素分泌缺陷、炎症、氧化应激等密切相关。课题组研究表明，经皮耳迷走神经刺激(Transcutaneous Auricular Vagus Nerve Stimulation, taVNS)可引起ZDF（Zucker Diabetic Fatty）大鼠短期血浆胰高血糖素(Glucagon, GC)、胰岛素、葡萄糖呈节律性释放，并对血糖、糖化血红蛋白(Glycosylated Hemoglobin, GHbAlc)和胰岛素具有长期的调控作用。本项研究通过基础实验阐释taVNS对IGT模型大鼠血糖的调节及胰岛素分泌、胰岛素受体(Insulin Receptors, INR)表达的作用机制；使用血糖试纸动态监测IGT模型大鼠的FPG及2hPG，Western Blot实验检测IGT模型大鼠下丘脑、肝脏、骨骼肌INR蛋白表达量；ELISA实验检测各组大鼠血浆GC、GHbA1c、胰岛素含量变化。通过多中心、随机对照临床试验，明确taVNS对IGT患者血糖水平和糖化血红蛋白浓度的影响。.研究表明：造模6周后，与正常组相比，模型组、taVNS组及耳缘-非迷走神经刺激(Transcutaneous Auricular non-Vagus Nerve Stimulation, tnVNS)组大鼠体质量、FPG及2hPG明显增加，表示IGT模型制备成功；taVNS干预4周后，与模型组相比，taVNS组大鼠体质量、FPG、2hPG、GC明显降低，血浆胰岛素含量和下丘脑、肝脏、骨骼肌的INR表达明显升高；与tnVNS相比，taVNS组大鼠FPG、2hPG降低，血浆胰岛素含量及下丘脑、肝脏中INR表达明显升高。.本研究证实了经皮耳迷走神经刺激治疗糖耐量受损的有效性及安全性，其效应机制可能是通过中枢及外周胰岛素受体表达等调节而介导的。