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给NIH孕鼠腹腔注射苯妥英钠(PHT)后观察腭裂发生率为22.4%,显示PHT对NIH小鼠只有致畸性,并测得胚胎内丙二醛(MDA)值显著增高(P<0.05),支持PHT致畸与自由基有关,揭示PHT可能通过增强前列腺素合成酶活性而导致自由基生成增多,但未见PHT对超氧化物歧化酶(SOD)有影响.维生素E(VitE)作为自由基清除剂能逆转PHT所致MDA值增高(P<0.05),而对SOD活性无明显影响.但过量的VitE与PHT合用反而使腭裂发生率增高。
The incidence of cleft palate in NIH pregnant mice was 22.4% after intraperitoneal injection of phenytoin sodium (PHT), showing that only PHT induced teratogenicity in NIH mice and the malondialdehyde (MDA) in embryos was significantly increased (P < 0.05), supporting the correlation between PHT teratogenicity and free radicals. It was revealed that PHT may increase the production of free radicals by enhancing the activity of prostaglandin synthase, but no effect of PHT on superoxide dismutase (SOD) was found. Vitamin E (VitE) as a free radical scavenger can reverse the PHT caused by increased MDA (P <0.05), while no significant effect on SOD activity. However, excessive use of VitE in combination with PHT instead increased the incidence of cleft palate.