右美托咪定对谷氨酸诱导的大鼠神经系统毒性作用的影响

摘要

目的 探讨右美托咪定(Dex)对大鼠谷氨酸神经毒性作用的影响及其机制.方法 采用脑室注射谷氨酸制作大鼠脑谷氨酸神经毒性模型,将36只SD大鼠随机分为对照组(C组)、谷氨酸损伤组(G组,脑室注射谷氨酸)、Dex1组(脑室注射谷氨酸前30 min腹腔注射Dex 50 μg/kg)和Dex2组(脑室注射谷氨酸前30 min腹腔注射Dex 100 μg/kg).2h后取脑,分离出右侧海马组织测定超氧化物歧化酶和丙二醛,剩余脑组织测定脑含水量.另用尼氏染色法检测神经细胞受损状态.结果 Dex1组和Dex2组的脑组织含水量、丙二醛水平比G组明显降低,超氧化物歧化酶明显升高.同G组相比,Dex1组、Dex2组海马尼氏染色结果显示神经细胞损伤减轻明显.结论 Dex预处理可以明显减轻谷氨酸介导的神经毒性作用,其机制可能是通过增加超氧化物歧化酶,抑制氧化应激反应从而拮抗谷氨酸引起的细胞神经毒性作用.%Objective To investigate the effects and mechanism of dexmedetomidine hydrochloride preconditioning against glutamate-induced neurotoxicity.Methods The model of glutamate-induced neurotoxicity was established by the injection of glutamate into lateral cerebral ventricle.Thirty-six SD rats were randomly divided into control group (C group),glutamate-induced neurotoxicity group (G group),Dex1 group and Dex2 group.Dex1 group and Dex2 group received intraperitoneal injection of dexmedetomidine respectively at a dose of 50 μg/kg or 100 μg/kg before glutamate application.Two hours later,the rats were sacrificed and hippocampus was separated to measure the level of SOD and MDA.The rest of each brain was used to measure the degree of brain edema.Pathological changes were observed under microscope with Nissl's staining.Results In contrast to G group,brain edema and MDA concentration in Dex1 group and Dex2 group were significant lower,while SOD concentrations were significantly increased and the pathological change in Dex1 group and Dex2 group were relieved obviously compared to glutamate-induced neurotoxicity group.Conclusion Dexmedetomidine preconditioning can significantly attenuate glutamate-induced neurotoxicity,which is properly related to the inhibition of oxidative-stress reaction.