异丙酚作用于孕中期大鼠对子代鼠学习记忆能力的影响

Effect of propofol exposure in mid-pregnancy on the learning and memory ability of the offspring rats

目的探讨异丙酚作用于孕中期大鼠对子代鼠学习记忆能力的影响。方法孕14 d SD大鼠30只,应用随机数字表法将其随机分为3组(n=10):质量分数为10%的脂肪乳对照组(A组)、75 mg·kg^(-1)异丙酚组(B组)和150 mg·kg^(-1)异丙酚组(C组)。所有大鼠均腹腔注射注入药物。Morris水迷宫实验评价子代鼠学习记忆能力,测定各组海马谷氨酸(glutamic acid,Glu)含量,Western blot法和RT-PCR法检测神经细胞凋亡相关蛋白水平及mRNA水平,包括Caspase-3、Bax、Bcl-2,以及检测蛋白激酶A(protein kinase A,PKA)/c AMP反应元件结合蛋白(c AMP response element binding protein,CREB)通路中PKA和CREB水平及mRNA水平。结果与A组比较,B、C两组逃避潜伏显著延长(P<0.01)、跨越平台次数显著减少(P<0.01);B、C两组海马Glu含量显著高于A组(P<0.01);与A组比较,B、C两组Caspase-3和Bax蛋白和mRNA表达均显著升高(P<0.01),Bcl-2、PKA、CREB蛋白和mRNA表达均显著下降(P<0.01)。结论异丙酚作用于孕中期大鼠会损害子代鼠的学习记忆能力。

Objective To investigate the effect of propofol exposure in mid-pregnancy about learning and memory in offspring rats. Methods On the 14 th day in pregnancy,30 Sprague-Daw le rats ere randomly divided into 3 groups（ n = 10） ： control group 10% fat emulsion（ Group A）,75 mg·kg^-1propofol group（ Group B） and 150 mg·kg^-1 propofol group（ Group C）. All rats received drugs intraperitoneally. The learning and memory ability of their offsprings ere evaluated by Morris ater maze,and glutamate（ Glu）content of hippocampus in each groups ere determined,Western blot analyses and Real-time PCR ere used to examine the apoptosis protein levels and mRNA levels of nerve cell,including Caspase-3,Bax,Bcl-2,and the protein kinase A（ PKA） and c AMP response element binding protein（ CREB） levels and mRNA levels of PKA / CREB pathw ays ere examined. Results Compared ith group A,the escape latency of group B and group C ere significantly longer than that of group A（ P〈0. 01）,the time of passing through the platform of group B and group C ere significantly less than that of group A（ P〈0. 01）. The glutamate of group B and group C ere significantly more than group A（ P〈0. 01）. Compared ith group A,the protein and mRNA expression of Caspase-3 and Bax of group B and group C had been significantly increased（ P〈0. 01）,the protein and mRNA expression of Bcl-2,PKA,CREB of group B and group C had been significantly decreased（ P〈0. 01）. Conclusions Propofol exposure during the mid-pregnancy has a damage effect on the learning and memory ability of the offspring rats.