多次异丙酚给药对大鼠海马pCREB表达的影响

Effects of repeated propofol administration on expression of hippocampal cAMP response element binding protein in rats

目的探讨多次异丙酚给药对大鼠海马磷酸化环磷酸腺苷反应元件结合蛋白（pCREB）表达的影响。方法雄性wistar大鼠48只，日龄18～21d，体重40～60g，随机分为4组，每组12只，各组分别腹腔注射0．9％生理盐水10ml／kg（A组）、异丙酚50mg／kg（B组）、异丙酚100mg/kg（C组）或异丙酚200mg／kg（D组），连续用药5d。每天均采用Morris水迷宫实验测试大鼠空间学习记忆能力。第5天测试结束后处死大鼠取脑分离海马组织，每组随机取6只应用免疫组织化学法检测海马pCREB的表达，剩余6只透射电镜下观察海马神经元突触结构。结果与第1天比较，各组第4、5天逃避潜伏期明显缩短（P〈0．05）；与A组比较，其余3组第4、5天逃避潜伏期延长（P〈0．05）；与B组比较，D组第5天逃避潜伏期延长（P〈0．05）；与A组和B组比较，C组和D组海马pCREB表达下调（P〈0．05）。随异丙酚剂量增加，大鼠海马神经元突触结构受损加重。结论多次较大剂量异丙酚给药可引起幼年大鼠空间学习记忆能力降低，其机制可能与海马pCREB表达下调、海马神经元突触结构改变有关。

Objective To investigate the effects of different doses of repeated propofol administration on the expression of hippocampal cAMP response element binding protein （CREB） in rats. Methods Forty-eight male Wistar rats aged 18-21 d weighing 40-60 g were randomly divided into 4 groups （ n = 12 each） ： control group （C） and 3 propofol groups （Pl , P2, P3 ）- The propofol groups received intraperitoneal propofol 50, 100 and 200 mg·kg^-1·d^-1 in a bolus or divided doses respectively for 5 consecutive days. The control group received normal saline instead of propofol. The spatial learning and memory ability was tested everyday at 2 h after the animals emerged from anesthesia using morris water maze （MWM）. The animals were killed on the 5th day after the test was finished and their hippocampi were immediately isolated for detection of pCREB expression by immunohistochemistry and microscopic examination of the ultrastructure of synapses between neurons with tansmission electron microscope. Results The latency of escaping was significantly shortened on the 4th and 5th day as compared with that on the 1st day in all the 4 groups. The latency of escaping was significantly increased by propofol in a dose-dependent manner on the 4th and 5th day as compared with control group. The hippocampal pCREB expression was significantly lower in group P2 and P3 than in control group and group P1. The structural damage to hippocampal synapses became more serious with the increasing propofol doses. Conclusion Repeated propofol administration can reduce spatial learning and memory ability in juvenile rats by down-regulating hippocampal pCREB expression and changing synaptic structure.