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

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

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。

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 feed ing 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 m[ 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 S100 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.