丙泊酚衍生物CQMU-039对全脑缺血再灌注模型大鼠脑损伤的保护作用

目的:研究丙泊酚衍生物CQMU-039对全脑缺血再灌注模型大鼠脑损伤的保护作用及其机制。方法:取大鼠48只,随机均分成模型组、丙泊酚组(丙泊酚注射液,100mg·kg-1)、假手术组和CQMU-039低、中、高剂量组(CQMU-039生理盐水溶液,20、50、100mg·kg-1),采用夹闭双侧颈总动脉合并低血压建立全脑缺血再灌注模型,术后30min腹腔注射相应药物,术后第8天观察各组大鼠空间学习记忆能力(以寻台潜伏期为指标)、海马组织形态变化及脑组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、神经生长因子β(NGF-β)、特导性半胱氨酸蛋白酶3(Caspase-3)活性的变化情况。结果:与模型组比较,丙泊酚组和CQMU-039中、高剂量组大鼠的寻台潜伏期明显缩短,脑组织中MDA、Caspase-3活性明显下降,SOD、NGF-β活性明显升高(P均<0.01);CQMU-039组大鼠海马组织损伤与剂量呈负相关。结论:CQMU-039可能通过提高机体清除自由基的能力、抑制细胞凋亡、增强神经营养等方面减轻全脑缺血再灌注模型大鼠的脑损伤而发挥保护作用。

Protection Effect of Propofol Derivative CQMU-039 on Global Cerebral Ischemia-reperfusion Injury of Rats

OBJECTIVE： To observe the protection effect of propofol derivative CQMU-039 on global cerebral ischemia-reperfusion injury in rats and its mechanism. METHODS： 48 rats were randomly divided into model group, propofol group （Propofol injection 100 mg·kg-1）, sham operation group and CQMU-039 low-dose, medium-dose and high-does groups （CQMU-039 normal saline solution , 20, 50, 100 mg·kg-1）. The global cerebral ischemia-reperfusion model was established by occlusion of bilateral common carotid artery. 30 minutes after operation each group was given relevant drugs. The spatial learning and memory ability of rats was observed 8 days after operation as well as the change of hippocampal tissue and the activity of SOD, MDA, NGF-β, Caspase-3 in cerebral tissue of rats. RESULTS： Compared with model group, the incubation period of propofol group and CQMU-039 medium-dose and high-dose groups had been improved significantly. The activity of MDA and Caspase-3 in cerebral tissue decreased significantly while the activity of SOD and NGF-β increased （P0.01）. The injury of hippocampal tissue in CQMU-039 groups had negative correlation with dose of drugs. CONCLUSION： Propofol derivatives CQMU-039 have some protection effect on cerebral ischemia-reperfusion brain injury by improving ability of scavenging free radical, inhibiting apoptosis, strengthening neurotrophy, etc.