Zhou Changwei, Sun Rong, Zhuang Sujuan, Sun Chongyi, Jiang Yongqing, Cui Yang, Li Shitou, Xiao Yanqiu, Du Yansheng, Gu Huiying, Liu Qingpeng
Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
Department of Outpatient OR, The 1st Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
Brain Res Bull. 2016 Mar;121:241-5. doi: 10.1016/j.brainresbull.2016.02.009. Epub 2016 Feb 11.
Metformin, a wildly used drug for type 2 diabetes, has recently been proven to protect a variety of cells from stress including stroke. Glutamate is an excitatory neurotransmitter that contributes to excitatory neuronal damage involved in stroke and neurodegenerative disorders. In this study, we demonstrated that pretreatment of rat cerebellar granule neurons (CGN) with metformin greatly enhanced cell viability against glutamate-induced neurotoxicity. Metformin significantly attenuated neuronal apoptosis in glutamate-treated CGN by reducing cytochrome c releasing, caspase-3 activation and phosphorylation of MAP kinases. Our results suggested that metformin was able to directly inhibit glutamate induced excitotoxicity in neurons and might be beneficial to patients suffered from stroke and neurodegenerative disorders.
二甲双胍是一种广泛用于治疗2型糖尿病的药物，最近已被证明可保护多种细胞免受包括中风在内的应激影响。谷氨酸是一种兴奋性神经递质，它会导致与中风和神经退行性疾病相关的兴奋性神经元损伤。在本研究中，我们证明用二甲双胍预处理大鼠小脑颗粒神经元（CGN）可显著提高细胞对谷氨酸诱导的神经毒性的生存能力。二甲双胍通过减少细胞色素c释放、半胱天冬酶-3激活和丝裂原活化蛋白激酶的磷酸化，显著减轻了谷氨酸处理的CGN中的神经元凋亡。我们的结果表明，二甲双胍能够直接抑制谷氨酸诱导的神经元兴奋性毒性，可能对中风和神经退行性疾病患者有益。
