电针调控线粒体动力学改善2型糖尿病大鼠骨骼肌胰岛素抵抗的磁共振波谱研究

Insulin resistance is one of the key pathological character as well as pathogenic factor of type 2 diabetes. Recent researches takes disorder of morphology and function of mitochondria (also called mitochondrial dynamics) as a decisive reason of the onset of insulin resistance. Mitochondrial dynamics becomes a new research direction of prevention and treatment of type 2 diabetes. Our previous researches showed that low frequency electro-acupuncture on EX-B3 and BL-20 can up-regulate skeletal muscle insulin signal pathway, and have intervention effects on insulin resistance. The underlying mechanism concerns regulation of skeletal muscle’s intake and oxidative decomposition of glucose. Based on these, the research takes ‘electro-acupuncture can improve mitochondrial dynamics to restore skeletal muscle mitochondria’s function, and relieve skeletal muscle insulin resistance caused by oxidative stress, and thereby treats type 2 diabetes’. It takes mitochondrial dynamics as breakthrough point, and observes electro-acupuncture’s effect on skeletal muscle mitochondria’s structure and function with transmission electron microscope and magnetic resonance spectroscopy, to provide a new mechanism of electro-acupuncture’s effect on hyperglycemia and insulin resistance of type 2 diabetes.

胰岛素抵抗是2型糖尿病重要病理特点和致病因素，最新研究发现线粒体结构、功能异常可能是胰岛素抵抗发生的重要原因。线粒体动力学因此成为2型糖尿病防治的新靶点。本课题组前期基础研究提示低频电针“胃脘下俞”、“脾俞”等穴位可以通过上调骨骼肌胰岛素信号通路，改善胰岛素抵抗。其机理涉及骨骼肌对葡萄糖的摄取和利用。基于此，本研究以“电针可通过改善线粒动力学，恢复骨骼肌线粒体氧化分解葡萄糖的能力，并改善氧化应激反应导致的骨骼肌胰岛素抵抗，调控2型糖尿病高血糖”为假说，以线粒体动力学为切入点，以电镜、磁共振波谱等技术观察低频电针对骨骼肌线粒体结构及其氧化葡萄糖能力的影响，为针灸调整2型糖尿病高血糖和胰岛素抵抗提供新的思路。

本研究以“电针可通过改善线粒动力学，恢复骨骼肌线粒体氧化分解葡萄糖的能力，并改善氧化应激反应导致的骨骼肌胰岛素抵抗，调控2型糖尿病高血糖”为假说，以线粒体动力学为切入点，以电镜、磁共振波谱等技术观察低频电针对骨骼肌线粒体结构及其氧化葡萄糖能力的影响，为针灸调整2型糖尿病高血糖和胰岛素抵抗提供新的思路。研究证实：电针可降低2型糖尿病大鼠血糖。其机制涉及对骨骼肌的胰岛素通路指标进行调整：（1）电针可改善骨骼肌摄取葡萄糖的能力，电针主要通过下调骨骼肌IRS-1 Ser307丝氨酸磷酸化的活性，促进IRS-1酪氨酸磷酸化，进而上调胰岛素信号通路，促进GLUT4膜移位，最终达到促进骨骼肌葡萄糖摄取，降低血糖的作用。（2）电针可改善骨骼肌代谢葡萄糖的能力：电针可显著降低模型动物骨骼肌中激增的ROS，减少氧化应激的程度，从而保护线粒体形态，使模型动物受损的线粒体形态得到一定程度的修复，同时维护线粒体功能，主要体现在提高β-ATP合成。