咪达唑仑对幼龄大鼠大脑神经元caspase-3活化的影响-陆军军医大学学报（原第三军医大学学报）

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Title:: Effect of Midazolam on caspase-3 activation of cerebral neurons in 7-day-old rats

Author(s):: WANG Guo-yi; TAO Guo-cai; YI Bin; CUI Jian; Department of Anesthesiology, Southwest Hospital, Third Military Medical University

摘要:: 目的观察咪达唑仑对幼龄SD大鼠大脑皮层神经元半胱氨酸天门冬氨酸蛋白酶-3活化（caspase-3 activation）的影响。方法出生7 d SD大鼠64只，雌雄不拘，分为A、B 2部分。A部分24只，分为4组（n=6）：A1为未给予咪达唑仑正常状态（记为0 min），A2、A3和A4按照18.0 mg/kg给予咪达唑仑后15、30、60 min 进行血气分析。B部分40只，分为5组（n=8）：对照组（B1）单次腹腔注射生理盐水18.0 mg/kg，B2、B3、B4、B5分别单次腹腔注射咪达唑仑4.5、9.0、13.5、18.0 mg/kg。给予咪达唑仑6 h后进行多聚甲醛灌注，取脑，进行caspase-3免疫组织化学染色与图像分析。结果咪达唑仑单次注射未发现幼龄SD大鼠产生缺血缺氧表现。单次给予咪达唑仑可导致幼龄SD大鼠大脑神经元caspase-3活化，给予较高剂量咪达唑仑后caspase-3活化强度明显增加。结论咪达唑仑可以促发幼龄SD大鼠大脑神经元caspase-3活化，并可能导致大脑神经元凋亡。

Abstract:: Objective To observe the effect of Midazolam on caspase-3 activation of cortical neurons in rat brain. Methods The experiment consisted of part A and part B, including 64 7-day-old Sprague Dawley rats of either sex. In part A 24 rats were randomly divided into 4 groups according to the time point when the arterial blood was collected after intraperitoneal injection of 18.0 mg/kg Midazolam(n=6 in each group), group A1 without Midazolam treatment as control, group A2 (15 min), group A3 (30 min), group A4 (60 min). In part B, 40 rats were randomly divided into groups B2-B5 (n=8 in each group) according to the dose of Midazolam (4.5, 9.0, 14.5, 18.0 mg/kg) and group B1 as control receiving 18.0 mg/kg normal saline. Both control and experimental rats were perfused transcardially with paraformaldehyde 6 h after Midazolam treatment, then their brains takenout were used for caspase-3 examination by immunohistochemistry. Results Single injection of Midazolam did not induce hypoxia/ischemia in 7-day-old SD rats, but led to the activation of caspase-3 in cerebral neurons. Furthermore, higher single dose of Midazolam enhanced the activation of caspase-3 more. Conclusion Midazolam triggers the activation of caspase-3 in cortical neurons and may lead to neuronal apoptosis.

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