丙泊酚及手术创伤对发育期大鼠神经发育和认知功能的影响

Effect of propofol and operative trauma on neurodevelopment and cognitive function of developing brain in rats

目的探讨丙泊酚及手术创伤对发育期大鼠神经发育和认知功能的影响及相关机制。方法 104只13日龄SD大鼠随机分为4组:对照组、丙泊酚组、手术组、丙泊酚+手术组。对照组腹腔注射7.5 mL/kg生理盐水后行假手术,丙泊酚组腹腔注射75 mg/kg丙泊酚,手术组行局麻下剖腹探查术,丙泊酚+手术组腹腔注射丙泊酚75 mg/kg+局麻剖腹探查术。术后各组随机分为两个亚组。其中一个亚组术后1 d检测幼鼠海马TNF-α的浓度,脑组织caspase-3、c-fos的表达。另一亚组饲养至60 d时行Morris水迷宫实验评估大鼠认知功能后检测大鼠海马TNF-α的浓度以及脑组织caspase-3、c-fos的表达。结果在13日龄幼鼠中,手术组TNF-α浓度、caspase-3、c-fos的表达较其他3组相比差异具有统计学意义(P<0.05)。对照组、丙泊酚组、丙泊酚+手术组3组之间TNF-α浓度、caspase-3、c-fos的表达差异无统计学意义(P>0.05)。在60日龄大鼠中,Morris水迷宫实验、TNF-α浓度、caspase-3、c-fos的表达,各组间差异无统计学意义(P>0.05)。结论局麻下手术创伤可导致幼年大鼠海马炎症反应加重,细胞凋亡增加,但该损伤不会持续至大鼠成年。而单次丙泊酚全麻对幼年大鼠大脑神经元发育无明显影响,且丙泊酚可缓解手术创伤所造成的幼鼠中枢炎症反应。

Objective To investigate the effect of propofol and operative trauma on the neurodevelopment and cognitive function of the developing brain and its mechanism.Methods A total of 104 postnatal day 13 Sprague-Dawley rats were randomly divided into 4 groups：control group（treated by 7.5 mL/kg saline and sham surgery）,propofol group（treated by 75 mg/kg propofol）,surgery group（with abdominal surgery under local anesthesia） and propofol ＋ surgery group（with abdominal surgery under local anesthesia plus 75 mg/kg propofol anesthesia）.Thirteen rats from each group were randomly selected for detecting the content of TNF-α in the hippocampus and the expression levels of caspase-3 and c-fos in the brain.Morris Water Maze test was used to detect the cognitive ability of the other rats at 60 days old,after which TNF-α content in the hippocampus and caspase-3 and c-fos expressions in the brain were detected.Results In 13 day-old rats,TNF-α level and caspase-3 and c-fos expressions differed significantly between the surgery group and the other 3 groups（P〈0.05） and were similar among the control group,propofol group and propofol＋surgery group（P〈0.05）.In 60-day-old rats,Morris water maze test results,TNF-α level or expressions of caspase-3 and c-fos showed no significant differences among the 4 groups.Conclusion Abdominal surgery can induce inflammation in the hippocampus and neuroapoptosis in neonatal rats rather than adult rats.Single-dose propofol anesthesia does not significantly affect neurodevelopment of young rats,and can relieve central inflammatory reaction induced by surgical trauma.