孕中期大鼠丙泊酚麻醉对其子代神经细胞的影响及可能机制

Effect of Propofol onNeurons of Rat Offspring after Propofol Exposure in the Second Trimester of Pregnancy

目的探讨孕中期大鼠丙泊酚麻醉对其子代神经细胞的影响及可能机制。方法孕14dSD大鼠24只,随机分成两组(n=12):对照组(C组)腹腔注射生理盐水(10mL/kg);丙泊酚组(P组)腹腔注射丙泊酚(80mg/kg),随后从尾静脉泵注40mg/(kg·h)丙泊酚2h。应用免疫荧光法检测用药5h后的胎鼠外侧神经节突起区(LGE)及新生鼠大脑海马区神经细胞Caspase-3的表达水平,使用(BrdU)免疫标记检测孕21d胎鼠及出生后30d子鼠海马室管膜下区(SVZ)及齿状回(DG)区神经细胞的增殖情况,免疫组织化学染色检测出生后30d子鼠前额皮质N-甲基-D-天冬氨酸(NMDA)受体亚单位NR1、NR2A、NR2B及突触后致密蛋白(PSD-95)的表达情况。结果 (1)与对照组相比,丙泊酚组孕14d胎鼠LGE区及新生鼠大脑海马区Caspase-3阳性细胞数明显增多(均P<0.01);(2)与对照组相比,丙泊酚组孕21d胎鼠海马SVZ及DG区的细胞增殖减少(均P<0.05);(3)与对照组相比,丙泊酚组出生后30d子鼠前额皮质NMDA受体亚单位NR1、NR2A、NR2B及PSD-95表达均降低(均P<0.01)。结论对孕中期大鼠实施丙泊酚麻醉可致其子鼠神经细胞凋亡增加及增殖减少,其机制可能与NMDA受体亚单位及PSD-95的表达异常有关。

Objective To investigate the effect of propofol on neurons in rat offspring and the possible mechanism after propofol exposure during the second trimester of pregnancy.Methods Twenty-four SD rats were randomly divided into two groups(n=12)on the 14th day of pregnancy:the control groupin which rats were intrapcritoncally injected with normal saline(10 mL/kg);the propofol groupin which rats were intrapcritoncally injected with propofol(80 mg/kg).followed by a 40 mg/(kg.h)propofol pump from the tail vein for 2 h.Immunohistochcniistry was used to detect the expression of cysteine aspartic acid-spccific protease 3(Caspase-3)in the lateral ganglionic emincnccCLGE.)of the fetal rats and the hippocampus of the neonatal rats 5 h after propofol exposun.T'he proliferation of neurons in the subvcntricular zonc(SVZ)and dentate gyrus(DG)was detected in 2 1 d fetal rats and 30 d neonatal rats by BrdU immunolabcling.Immunostaining was used to detect N-mcthyl-D-aspartate(NMDA.)receptor subunitsNR1,NR2 A,NR2B and postsynaptic dense protcin(PSD-95)in the prefrontal cortex of 30 d neonatal rat..Results The number of caspase-3 positive cells was significantly increased in the LGE of 14 d fetal rats and in the hippocampus of neonatal rats in the propofol group as compared with the control group(P<0.01);the proliferation of neuronal cells was significantly decreased in the SVZ and DG of 21 d fetal rats in the propofol group as compared with the control group(P<0.05);the expression levels of NMDA receptor subunits and PSD-95 were significantly reduced in the prefrontal cortex of 30 d neonatal rats in the propofol group when compared with the control group(P<0.01).Conclusion Propofol exposure during the second trimester of pregnancy could result in the increase of neuron apoptosis and decrease of neuron proliferation in rat offsprings which is associated with the abnormal expression of the subunits of NMDA receptor and PSD-95.