褪黑素通过线粒体途径对糖尿病脑病突触可塑性的影响

Effect of Melatonin on Synaptic Plasticity in Diabetic Encephalopathy via Mitochondrial Pathway

目的观察褪黑素对糖尿病脑病中线粒体功能及突触可塑性的影响,探讨褪黑素治疗糖尿病脑病的具体机制。方法腹腔注射链脲佐菌素建立糖尿病小鼠模型,造模前、造模3 d和12周分别检测小鼠体重和血糖变化。ELISA检测TNF-α和IL-6炎症因子含量。线粒体膜电位和线粒体呼吸链试剂盒检测小鼠海马组织线粒体功能。Western Blot检测线粒体自噬蛋白以及海马突触可塑性相关蛋白的表达。结果与CON组相比,DM组小鼠体重明显降低(P<0.01),血糖浓度升高(P<0.01),TNF-α和IL-6因子含量增加(P<0.01),线粒体膜电位及复合物Ⅰ、复合物Ⅱ和复合物Ⅳ活性明显降低(P<0.01),海马组织自噬蛋白LC3和Beclin及突触蛋白SYN和PSD95蛋白表达明显降低(P<0.01),给予褪黑素干预后明显改善上述变化。结论褪黑素可能通过改善线粒体功能,减缓对糖尿病小鼠海马突触可塑性的损伤,参与及改善糖尿病脑病的发生与发展。

Objective To observe the effects of melatonin on mitochondrial function and synaptic plasticity in diabetic encephalopathy and to explore the specific mechanisms of melatonin treatment for diabetic encephalopathy.Methods The diabetic mouse model was established by intraperitoneal injection of streptozotocin,and changes in body weight and blood glucose were detected before modeling,3 days and 12 weeks of modeling,respectively.The levels of TNF-α and IL-6 inflammatory factors were detected by ELISA.Mitochondrial membrane potential and mitochondrial respiratory chain kit were used to detect mitochondrial function in mouse hippocampus.Western Blot was used to detect the expression of mitochondrial autophagy proteins as well as hippocampal synaptic plasticity-related proteins.Results Compared with the CON group,mice in the DM group had significantly lower body weight(P<0.01),higher blood glucose concentration(P<0.01),increased levels of TNF-α and IL-6 factors(P<0.01),significantly lower mitochondrial membrane potential and activities of complex Ⅰ,Ⅱ and Ⅳ(P<0.01),and significantly lower expression of autophagy proteins LC3 and Beclin and synaptic proteins SYN and PSD95 in hippocampus.However,the above changes were significantly improved after melatonin intervention.Conclusion Melatonin may reduce the damage of hippocampal synaptic plasticity in diabetic mice by improving mitochondrial function,and participate in and improve the occurrence and development of diabetic encephalopathy.