丙泊酚对高脂血症大鼠空间学习记忆功能的影响及机制

THE EFFECT AND MECHANISMS OF PROPOFOL ON LEARNING AND MEMORY FUNCTION OF SPACE IN HYPERLIPIDEMIC RATS

目的:研究丙泊酚对高脂血症大鼠空间学习记忆功能和海马神经元Tau蛋白磷酸化表达水平及老年斑沉积的影响。方法:将成模大鼠随机分成4组:P10、P30、P75组分别腹腔注射丙泊酚(10,30,75mg/kg·d-1),对照组(G组)给予生理盐水75mg/kg·d-1,连续注射5d。Morris水迷宫测试大鼠空间学习记忆功能。取海马组织行刚果红和免疫组织化学染色,ipwin32软件分析Tau蛋白磷酸化表达阳性细胞平均光密度值。结果:定位航行实验及附加实验:P30、P75组逃避潜伏期较P10、G组明显延长(P<0.05);空间搜索实验:P30、P75组穿越平台次数较P10、G组明显减少(P<0.05);免疫组织化学染色:P30、P75组平均光密度值与P10、G组比较,差异有统计学意义(P<0.05)。刚果红染色:P30、P75组可见老年斑沉积物。结论:镇静或麻醉剂量丙泊酚可损害高脂血症大鼠空间学习记忆能力。其机制可能与海马老年斑沉积增多和Tau蛋白过度磷酸化相关。

Objective：To study the effects of propofol on learning and memory function of space and the expressive level of phosphorylated protein Tau and senile plaque deposition in hippocampal neurons of hyperlipidemic rats.Methods：The animal model was randomly divided into P10,P30,P75 and control groups.P10,P30 and P75 groups were intraperitoneal injected of propofol （10,30 and 75 mg/kg · d-1; respectively）,and control group received intraperitoneal injection of 75 mg/kg · d-1 normal saline for 5 days.Spatial learning and memory function in rats were determined with Morris water maze tests.The hippocampus was stained by Congo red staining and immunohistochemical staining.The average optical density value of positive cells （expression of phosphorylated protein Tau） was analyzed by ipwin32 software.Results：The escaped latency was longer in P30 and P75 groups than in P10 and control groups （P 〈0.05）.The times of crossing the platform were less in P30 and P75 groups than in P10 and control groups （P 〈0.05）.The average optical density in P30 and P75 groups was different from that in P10 and control groups （P 〈0.05）.Congo red staining showed that the senile plaque deposits were seen in P30 and P75 groups.Conclusion：The dose of propofol under sedation or anesthesia can damage the ability of learning and memory space on hyperlipidemic rats.The mechanism may be related to the increase of hippocampal senile plaque deposition and the high expression of Tau phosphorylation.