咪达唑仑对幼年小鼠惊厥性脑损伤的作用

Effects of midazolam on convulsive brain injury in young mice

目的本研究通过阐述咪达唑仑对幼年小鼠惊厥性脑损伤的影响,为临床预防和治疗小儿惊厥性脑损伤提供一定的理论依据。方法将80只19 d幼年小鼠随机分为正常对照组、生理盐水组、低剂量咪达唑仑组、中剂量咪达唑仑组、高剂量咪达唑仑组五组,每组16只,分别注射生理盐水或咪达唑仑后20 min,腹腔注射罗哌卡因,观察惊厥发生分级,并记录惊厥出现时间和持续时间;利用脑立体定位仪进行电极植入,记录各组脑电图变化情况。提取惊厥后24 h生理盐水模型组和咪达唑仑低、高剂量组海马组织RNA,采用QPCR检测神经营养因子S100β和GFAP,观察咪达唑仑对幼鼠脑损伤的作用。结果中、高剂量组与生理盐水组相比,小鼠惊厥发生率明显下降,低剂量组与生理盐水组比较差异无统计学意义(P>0.05)。小鼠脑电图显示:生理盐水对照组病理样的脑电波表现为尖波、棘波,多棘-慢复合波,波幅为200~250μV,通常持续4 s以上;低、中高剂量咪达唑仑组脑电异常波较生理盐水组逐渐减少,波幅亦减少,持续时间缩短。高剂量组S100β和GFAP mRNA表达明显低于生理盐水对照组(P<0.05)。结论咪达唑仑促使惊厥性脑损伤小鼠的脑电图异常波的减少,波幅减低,持续时间减少,降低脑损伤相关分子的表达,可能对小儿惊厥性脑损伤的治疗提供一定的帮助。

Objective To elaborate the effect of midazolam on convulsive brain injury in young mice to provide a certain theoretical basis for the clinical prevention and treatment of convulsive brain injury in children.Methods Eighty 19 d old young mice were randomly divided into the normal control group,normal saline group,low dose midazolam group,medium dose midazolam group,and high dose midazolam group,16 cases in each group.At 20 min after the injection of normal saline or midazolam respectively,the intraperitoneal injection of ropivacaine was performed.The grade of convulsion was observed.The appearing time and persistent time of convulsion were recorded.The electroencephalogram(EEG)changes of each group were recorded by electrode implantation with stereotactic brain localizer.The hippocampal tissue RNA in the normal saline model group,midazolam low and high doses groups was extracted at 24 h after convulsion.Q-PCR was adopted to detect S100βand GFAP expressions.The effect of midazolam on the brain injury in young mice was observed.Results The occurrence rate of mice convulsion in the medium and high doses groups was significantly decreased compared with the normal saline control group,while there was no statistically significant difference between the low dose group and the normal saline control group(P>0.05).The mice EEG showed that the pathological brainwaves in the normal saline control group were manifested by sharp wave,spike wave,multi-spike and slow complex wave with an amplitude of 200-250μV,usually lasting for more than 4 s.Compared with the normal saline group,the EEG abnormal waves in the low,medium and high doses midazolam groups were gradually reduced,the wave amplitude was decreased and the persistent time was also shortened.The S100βand GFAP expression levels in the high dose group were significantly lower than those in the normal saline control group(P<0.05).Conclusion Midazolam promotes the abnormal EEG waves to decrease,reduce the wave amplitude and persistent time in convulsive brain injury mice,as well as decrease the expression of the brain injure-associated molecules,which may provide a certain help for the treatment of pediatric convulsive brain injury.