氟桂利嗪和拉莫三嗪对胎鼠缺血缺氧性脑损害的保护作用

目的研究氟桂利嗪(FNZ)、拉莫三嗪(LTG)及两药联合经孕鼠给药,对胎鼠宫内缺血缺氧性脑损害的保护作用。方法将孕20 d Wistar大鼠40只,随机均分为FNZ组、LTG组、FNZ LTG组和对照组。前3组大鼠于脑缺血缺氧术前3 d开始灌胃给药,每天1次,分别为FNZ 0.5 mg/(kg.d),LTG 10 mg/(kg.d),FNZ 0.5 mg/(kg.d) LTG 10 mg/(kg.d)。第3天给药后3 h,每组取8只孕鼠制作宫内缺血缺氧模型,剩余2只孕鼠直接行剖宫产取胎鼠,每胎5只。于缺血缺氧后6、12、24、48 h分别取胎鼠血清0.5 ml,采用ELISA法测定血清神经元特异性烯醇化酶(NSE)和酸性钙结合蛋白(S-100)水平。结果胎鼠缺血缺氧后,血清NSE和S-100水平明显升高。FNZ组、LTG组及FNZ LTG组胎鼠缺血缺氧后各个时间点血清NSE和S-100较对照组明显降低,差异均有极显著性意义(均P<0.01)。联合用药组效果更明显,组间比较差异亦有极显著性意义(P<0.01)。结论产前预防性灌胃FNZ、LTG对胎鼠宫内缺血缺氧性脑损伤具有保护作用,联合用药效果更明显。

Neuroprotective Effects of Flunarizine and Lamotrigine on Hypoxic-ischemic Brain Damage in Fetal Rats

Objective To investigate the neuroprotective effects of flunarizine(FNZ),lamotrigine(LTG) or combined use of them on hypoxic-ischemic brain damage in fetal rats.Methods Forty pregnant Wistar rats(pregnancy for 20 days) were randomly assigned into FNZ group,LTG group,FNZ LTG group and control group.Drugs were administered through feeding tube 3 days before the hypoxic-ischemic operation once a day.The dosages to the first three groups respectively were: FNZ 0.5 mg/kg every day,LTG 10 mg/kg every day,and FNZ 0.5 mg/kg every day LTG 10 mg/kg every day respectively.Three h after the third dose,fetal rats hypoxic-ischemic brain damage model was established in 8 cases of pregnant rats from each group,and remaining 2 rats served as controls.Five fetal rats were taken out from each pregnant rat.0.5 ml serum was taken from fetal rats 6,12,24,and 48 h respectively after the birth.The concentrations of neuro specific enolase(NSE) and S-100 protein(S-100) in serum were detected by enzyme immunoassay method.Results The concentrations of serum NSE and S-100 protein in hypoxic-ischemic fetal rats were markedly higher than those in no ischemic group.The concentrations of serum NSE and S-100 protein in FNZ group,LTG group and FNZ LTG group were statistically significantly lower than those in control group(all P<0.01),and there was significant difference between combined drug group and single drug group(P<(0.01).) Conclusion Preventive antenatal oral FNZ and LTG have positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage.The effects of combined use of them were more satisfactory.