硫酸镁对脑缺血早期脑组织中Ca^(2+)、Mg^(2+)和谷氨酸含量及谷氨酸受体1表达的影响

MgSO_4 lessens cerebral-ischemic damage by decreasing infarct size,Ca^(2+) and glutamate content and expression level of NMDA receptor-1 and increasing Mg^(2+) content in cerebral cortex of rats

目的:探讨不同时间、不同剂量硫酸镁对大鼠永久性局灶性脑缺血损伤后神经功能的保护作用。方法:用线栓法制作Wistar大鼠左侧大脑中动脉栓塞模型,实验设正常组、假手术组、局灶性脑缺血组(MCAO组)和MgSO4治疗组。MCAO组又分为3、6、12、24和48 h这5个时间点;MgSO4治疗组分为单次治疗1组、单次治疗2组、双次治疗1组、双次治疗2组和双次治疗3组。分别于脑缺血损伤后不同时间进行神经功能评分、脑梗死体积、Ca2+、Mg2+和谷氨酸含量的测定及谷氨酸受体1表达水平的检测。结果:硫酸镁治疗组与MCAO组相比,神经功能恢复好,梗死灶体积缩小,脑皮质Ca2+和谷氨酸含量明显下降,Mg2+含量显著上升。同时,谷氨酸受体1的表达水平也降低。治疗效果:单次治疗2组优于单次治疗1组,双次治疗组又优于单次治疗组,其中双次治疗1组效果最为显著。结论:硫酸镁对脑缺血损伤有明显的神经保护作用,且治疗效果与治疗时间早晚和剂量大小密切相关。

To investigate the neuroprotective effects of MgSO4 in different doses at varying stages after permanent focal cerebral ischemia. METHODS： The rat models of permanent left middle cerebral occlusion （MCAO） were established with the suture method. The Wistar rats were divided into normal group, sham-operated group, MCAO group and MgSO4-therapy groups. MCAO group was set for five-time points： 3, 6, 12, 24 and 48 h; MgSO4-therapy groups were divided into Single 1 （30 min before MCAO injecting 60 mg·kg^-1 group）, Single 2 （30 min before MCAO injecting 120mg·kg^-1 group）, Double 1 （30 min before and 1 h after MCAO injecting 120 mg·kg^-1 group）, Double 2 （1 h before and 3 h after MCAO injecting 120 mg·kg^-1 group） and Double 3 （3 h before and 5 h after MCAO injecting 120 mg·kg^-1 group）. Neurological deficit examination, infarct volume,calcium ion （Ca^2＋ ）, magnesium ion （Mg^2＋ ） and glutamate content, and the expression levels of NMDA receptor 1 in cerebral cortex were detected at different time points in all animals. RESULTS： Compared with MCAO group, MgSO4 decreased infarct size, Ca^2＋ and glutamate contents, and increased Mg^2＋ content in cerebral cortex and improve neurological score. Meanwhile, expression levels of NMDA receptor-1 were significantly down-regulated. Therapeutic effects of double were better than that of single, moreover, double 1 had the optimal action. CONCLUSION： MgSO4 has remarkable neuroprotective effects and its therapeutic efficacy was intimately associated with the dose dependent and ischemic duration.