中文摘要
在前期支持下,我们发现重建氧化-还原平衡,改善线粒体功能,可恢复老年动物内源性保护效应,而且电针可促进GSK-3β磷酸化,调节线粒体凋亡路径和抗氧化能力,减轻糖尿病脑缺血损伤,相关结果在Mol Neurobiol等发表11篇SCI论文。糖尿病导致了线粒体功能紊乱与降低,恢复线粒体功能是治疗糖尿病的有效治疗策略,我们发现电针可上调糖尿病小鼠脑缺血后NRF-1和TFAM的表达,增加ATP产生,改善线粒体功能,抑制GSK-3β磷酸化可逆转电针的作用。本项目拟进一步研究针刺调节线粒体功能的机制,证实“针刺通过GSK-3β磷酸化,调节PGC-1α转录后修饰(磷酸化/乙酰化),增强线粒体生物发生,改善线粒体功能从而减轻糖尿病脑缺血损伤”的假说,有助于回答糖尿病脑组织对缺血损伤更为敏感等科学问题,也将为预防和治疗糖尿病缺血性脑卒中提供新的思路及治疗靶点。
英文摘要
Under the support of previous grant (No. 81228022), we discovered that rebuilding the balance of oxidative and anti-oxidative could improve mitochondrial function and restore endogenous protective effect in the old rat. In addition, Electroacupuncture induces cerebral ischemic tolerance through glycogen synthasekinase-3β (GSK-3β) phosphorylation,which can regulate mitochondrial cellular apoptosis and activate antioxidant system against oxidative stress in normal rats and diabetic mice. Eleven related SCI research articles were published on Mol Neurobiol etc. Diabetes mellitus caused mitochondrial dysfunction, modulating mitochondrial function has therefore emerged as an attractive therapeutic strategy for Diabetes mellitus. Our previous research discovered that Electroacupuncture up-regulated the expression of NRF-1 and TFAM in diabetic mice after cerebral ischemia, increased the production of ATP and improved mitochondrial function, which can reversed by the inhibition of GSK-3β phosphorylation. According to the above evidence, this project to explore the regulation mechanism of Electroacupuncture on mitochondrial function, we propose that electroacupuncture could induce the post-translational modifications of PGC1-α (phosphorylation/acetylation) by GSK-3β phosphorylation. Then, enhanced mitochondrial biogenesis and improved mitochondrial function, which can induce cerebral ischemic tolerance and reduce the nerve injury after ischemic stroke in diabetic mice. This can help answer the scientific problems such as why diabetes brain is more sensitive to ischemic injury, which will also provide new ideas and therapeutic targets for the prevention and treatment of diabetes cerebral ischemia.
