产前预防性用药对胎鼠缺血缺氧性脑损伤血清CK-BB含量的影响

Effects of antenatal flunarizine,lamotrigine on changes of serum CK-BB in fetal rats after hypoxic-ischemic brain damage

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20d 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3d开始灌胃给药,每天1次,分别为FNZ0.5mg/(kg.d),LTG10mg/(kg.d),FNZ0.5mg/(kg.d)+LTG10mg/(kg.d)。第3天给药后3h,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、48h分别取胎鼠血清0.5mL,采用电化学发光法测定血清磷酸肌酸激酶脑型同工酶(CK-BB)水平。结果胎鼠缺血缺氧后,血清CK-BB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CK-BB较对照组明显降低,差异均有极显著意义(均P<0.01)。联合用药较单个药物应用效果更明显,组间比较差异亦有极显著意义(P<0.01)。结论产前预防性口服FNZ、LTG对胎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） and lamotrigine （LTG）, and their combination on the hypoxic-ischemic brain damage in fetal rats. Methods Forty cases pregnant Wistar rats （ pregnancy for 20 days） were randomly assigned into FNZ group, LTG group, FNZ ＋ LTG group and the control group. The drugs were administered through feeding tube 3 days before the hypoxic-ischemic operation once a day. The dosages in the three study groups were： FNZ 0.5 mg/（kg· d）, LTG 10 mg/（kg· d）, FNZ 0.5 mg/（kg· d） ＋ LTG 10 mg/ （kg· d）, respectively. Three hours after the third dose, 8 cases of pregnant rats from each group were operated on for the fetal rats hypoxic-ischemic brain damage model, 2 cases as the control, and 5 fetal rats were taken out from each pregnant rat. The serum （0.5 mL） was taken from the fetal rats 6, 12, 24, 48 h after the birth, respectively. The concentration of brain-specific creatine kinase （CK-BB） in serum was detected by the electrochemistry radiation method. Results The concentrations of serum CK-BB in hypoxic-ischemic fetal rats were significantly higher than those in the no ischemic group. The concentrations of serum CK-BB in FNZ group, LTG group, FNZ ＋ LTG group were distinctively lower than those in the control group, there were significant differences among the four groups and between the combineddrug group and the single - drug group, P 〈 0.01. Conclusions Antenatal oral FNZ and LTG have positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The effects of the combination of the two drugs are much better.