孕期氯氮平暴露对子代大鼠生长发育和脑MAPK44／42表达的影响

Effect of clozapine exposed in the pregnant day on the development and the expression of MAPK44/42 in brain of filial rats

目的建立孕期氯氮平暴露子代大鼠模型，观察孕期给药对子代造成的影响。方法8周龄wistar雌鼠，分为对照组（n=17只）和用药组（n=25只），在大鼠孕6—15d，对照组腹腔注射生理盐水，用药组注射氯氮乎针剂，观察子代大鼠体格发育、神经反射、神经行为以及脑MAPK表达。结果氯氮平孕期暴露组导致子代大鼠早期生长延迟，出生后第4天和第7天（F=12．56／7．51，P〈0．01）体质量增长低于对照组；神经发育指标显示悬崖回避反射在出生后第3天和第9天（F=4．969／4．348；P〈0．05）与对照组相比回避反应时间延长；空中翻正反射达标数目较对照组明显减少（F=7．959／6．457，P〈0．01／0．05）：旷场行为试验未显示差异性；对出生后15d龄的子代大鼠海马及其前额叶皮质MAPK44／42表达检测显示：海马部位Pho—MAPK44／42表达显著低于对照组（F=18．729／23．824，P〈0．01），MAPK44／42表达2组差异无显著性；前额叶皮质Pho—MAPK44／42和MAPK44／42表达2组差异无显著性。结论孕期氯氮平暴露可导致子代大鼠生长发育和脑发育异常。

Objective To set up the experimental animal model of the filial rats exposed clozapine in the pregnant day and expect to know what is the effect on the offspring exposed the antipsychiatrie in gestation. Methods Female Wister rats were divided into both the control group （ n = 17） and clozapine group （ n = 25 ） which were intraperitoneally injected saline and clozapine respectively from pregnant day 6 to day 15, and their pup rats were examined development indexes such as the physical growth, neural reflex, neural behavior and the expression of MAPK44/42 in brain in neonatal stage. Results it was shown that clozapineexposed in pregnant day lead to the retardation of the weight of filial rats in earlier age such as postnatal day 4 （ PND4 ） and PND7 （F = 12.56/ 7.51, P= 0. 001/0. 008 ）. As for neural reflex, the time of cliff avoidance of rats was significantly delayed in PND 3 and day 9 （F = 4. 969/4. 348 ; P = 0.03/0.041 ）, and the ratio of positive response of air righting decreased compared with the control group in PND13 and PND15 （F=7. 959/6. 475, P=0.007/0. 016）. There was no difference between two groups on the behavior of the filial rats in the open field of filial rats. The expression of Pho- MAPK44/42 in hippocampi of exposed-clozapine offspring in PND15 was significantly lower than the control＇ s （F = 18. 729/23. 824, P=0. 001 ） ,however, no difference was demonstrated on the expression of MAPK44/42 in hippocampi as well as the expression of both Pho-MAPK44/42 and MAPK44/42 in forehead cortex in two groups. Conclusion The resuits suggest the aberration of both physical and mental development of fihal rats exposed clozapine in gestation.