目的：宫内发育迟缓(IUGR)患儿常有脑发育的异常。川芎嗪能改善脑部微循环,已被应用于新生儿缺氧缺血性脑损伤的治疗。被动吸烟法造大鼠IUGR模型,母鼠在孕8～20d给予川芎嗪,了解其对胎鼠宫内发育迟缓及其脑发育的影响,并探讨其作用机理。方法：孕鼠随机分为4组(均n=9):对照组,模型组,小剂量(40mg/kg)川芎嗪治疗组、大剂量(80mg/kg)川芎嗪治疗组。后3组孕鼠予以被动吸烟导致胎鼠宫内发育迟缓。孕21d剖宫取胎,观测胎鼠体重、脑重、肝重、身长及尾长;检测胎鼠脑组织中一氧化氮(NO)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性。结果：对照组、模型组与小剂量、大剂量川芎嗪治疗组胎鼠IUGR发生率分别为3.9%(4/105),55.0%(50/106),11.8%(11/103)和5.4%(5/99)。模型组胎鼠体重(3.1±0.3gvs3.8±0.6g)、脑重(0.144±0.012gvs0.176±0.018g)、肝重(0.29±0.06gvs0.34±0.07g)均较对照组明显降低,差异有显著差异(均P<0.01),小、大剂量川芎嗪治疗组与模型组相比各指标均有所改善。模型组胎鼠脑组织NO(52.4±1.4μmol/gvs43.7±6.7μmol/g)和MDA(273.5±8.5μmol/gvs249.6±6.2μmol/g)水平较对照组明显增高(均P<0.01),而SOD活性比对照组明显降低29.7±2.6U/mgvs36.5±3.9U/mg(P<0.01)。川芎嗪治疗组与模型组相比,MDA水平降低而SOD活性增高(均P<0.01),较模型组进一步增高。结论：川芎嗪可有效防治被动吸烟诱导的胎鼠IUGR及其脑发育障碍,其机制可能与其纠正机体的氧化与抗氧化失衡有关。

OBJECTIVE: Intrauterine growth retardation (IUGR) may contribute to the disorder of brain development of fetuses. Because ligustrazine has been proved to be effective in improving blood circulation and relieving clot formation, it has been used to treat hypoxic-ischemic brain damage of the newborn. This study aimed to explore the effect of ligustrazine on the brain development in fetal rats with IUGR induced by passive smoking and its mechanism. METHODS: Thirty-six pregnant rats were randomly assigned into four groups: Control, Model, Low dose (40-mg/kg ligustrazine) and High dose (80-mg/kg ligustrazine) (n=9 each). IUGR was induced by passive smoking in rats from the last three groups. Ligustrazine was administered for the last two groups between day 8 and day 20 of gestation. On day 21 of gestation, the fetal rats were delivered by cesarean section. The body weight, brain weight, liver weight, body length and tail length of fetal rats were measured. The levels of nitric oxide(NO), malondialdehyde(MDA) and superoxide dismutase(SOD) activity in the brains of fetal rats were examined. RESULTS: The incidence of IUGR in the Control, Model, and the Low and High dose ligustrazine treated groups was 3.9%(4/105), 55.0%(50/106), 11.8%(11/103) and 5.4%(5/99) respectively. The average body weight(3.1±0.3-g vs 3.8±0.6-g), brain weight (0.144±0.012-g vs 0.176±0.018-g)and liver weight (0.29±0.06-g vs 0.34±0.07-g)of fetal rats in the Model group were all significantly lower than those of the Control group(P<0.01). Those in the two treatment groups were significantly higher than in the IUGR group. The levels of NO (52.4±1.4-μmol/g vs 43.7±6.7-μmol/g)and MDA (273.5±8.5-μmol/g vs 249.6±6.2-μmol/g)in the brains of fetal rats of the Model group increased significantly compared with those of the Control group(both P<0.01), but the activity of SOD of the Model group decreased compared with the Control group(29.7±2.6-U/mg vs 36.5±3.9-U/mg)(P<0.01). In the Ligustrazine treated groups, the levels of MDA decreased and the levels of SOD activity increased compared with the Model group(both P<0.01), but the levels of NO were higher than those of Model group. CONCLUSIONS: Administering ligustrazine during pregnancy can decrease the incidence of fetal IUGR induced by passive smoking and improve the brain development of fetal rats. The effect of ligustrazine works possibly by redressing the unbalance between oxidate and antioxidate system.