异丙酚对谷氨酸诱导大鼠海马神经元损伤的影响

Effects of propofol on cultured hippocampal neurons injured by glutamic acid

目的观察异丙酚对谷氨酸诱导体外培养大鼠海马神经元损伤的影响。方法酶消化法分离Wistar新生大鼠海马,培养12 d的海马神经元随机分为三组(n=5),正常对照组(Con组)、谷氨酸100 μmol/L孵育24 h组(Glu组)、谷氨酸100 μmol/L孵育24 h后异丙酚500 μmol/L再孵育24 h组 (Pro-Glu组)。四甲基氮唑蓝法测定细胞存活率,免疫细胞化学法测定c-fos蛋白表达,流式细胞仪测定细胞凋亡率。结果与Con组比较,Glu组及Pro-Glu组的细胞存活率下降,c-fos蛋白在细胞核内表达呈紫黑色且数量增加,细胞凋亡率增高(P<0．05或0．01);与Glu组比较,Pro-Glu组c-fos阳性蛋白减少,细胞凋亡率降低,细胞存活率增高(P<0．05)。结论异丙酚通过降低细胞凋亡率和c-fos阳性蛋白表达,提高细胞存活率,对谷氨酸诱导的海马神经元损伤起一定保护作用。

Objective Propofol has been found to have anti-lipid peroxidation effect. We aimed to evaluate the effects of propofol on primarily cultured hippocampal neurons injured by glutamic acid. Methods Hippocampal neurons were obtained from newborn Wistar rats （within 24 h after birth） and cultured for 12 days. The 12 d cultured hippocampal neurons were randomly divided into three groups ： （1） control group; （2） glutamate group in which cells were incubated with glutamate 100 μmol/L^-1 for 24 h ; （3） propofol-glutamate group in which cells were incubated with propofol 500μmol/L^-1 and glutamate 100μmol/L^-1 for 24 h. Cell survival rate （MTT）, apoptosis （flow cytometry） and C-fos protein （immuno-histochemistry） production were determined in each group. Results C-fos protein and apoptosis were significaotly increased and survival rate was decreased in glutamate group compared with those in control group （P〈0.01）. In propofol-glutamate group propofol reduced C-fos protein, decreased apoptosis in the cells and increased survival rate compared with those in glutamate group （P 〈 0.05, 0.01 ）. Conclusion Propofol antagonizes the neurotoxic action of excitatoy amino-acid.