肼苯哒嗪减轻创伤性脑损伤后的认知功能障碍

Hydralazine alleviates cognitive impairment after traumatic brain injury

目的探讨丙烯醛(Acr)清除剂肼苯哒嗪(Hyd)对创伤性脑损伤(TBI)后认知功能障碍的治疗作用及其可能机制。方法先将成年(6~8周)C57BL/6雄性小鼠随机分为假手术组(Sham组)和TBI后不同时间点(术后3、7、14、28 d)4个亚组,通过Western blotting检测海马区Acr水平的变化情况,然后再将小鼠随机分为Sham组、TBI组和TBI+Hyd(Acr清除剂)干预组,分别通过Morris水迷宫实验、Western blotting以及ELISA检测技术等评估各组小鼠的认知功能、神经突触蛋白的表达量以及线粒体生物发生等变化。结果与Sham组相比,TBI后小鼠海马区Acr水平显著增高。给予Hyd干预能有效减轻小鼠TBI后的认知功能障碍、升高突触相关蛋白的表达水平。并且Hyd治疗明显改善海马区线粒体生物发生和能量代谢,可能是其发挥保护作用的重要机制之一。结论Hyd治疗可促进TBI后海马区线粒体生物发生的恢复,减轻海马神经元的结构与功能损伤,从而改善TBI后的认知功能障碍。

Objective To investigate the protective effect of acrolein(Acr)scavenger hydralazine(Hyd)on cognitive impairment after traumatic brain injury(TBI)and its related mechanism.Methods Adult(68 weeks)male C57BL/6 mice were randomly divided into sham operation group(Sham group)and four subgroups at different time points after TBI(3,7,14 and 28 d after operation).The changes of Acr level in hippocampus were detected by Western blotting.Then the mice were randomly divided into Sham group,TBI group and TBI+Hyd intervention group.The changes of cognitive function,expression of synaptic proteins and mitochondrial biogenesis were evaluated by Morris water maze test,Western blotting and ELISA.Results Compared with the Sham group,the level of Acr in the hippocampus significantly increased in the TBI group.Hyd intervention effectively reduced the cognitive impairment in mice after TBI,and increased the levels of synapse-related proteins.Moreover,Hyd treatment significantly improved mitochondrial biogenesis and energy metabolism in the hippocampus,which might be one of the important mechanisms exerting its protective effect.Conclusion Hyd treatment can promote the recovery of mitochondrial biogenesis in the hippocampus after TBI,reduce the structural and functional damage of hippocampal neurons,and improve the cognitive function after TBI.