孕期暴露苯并[a]芘对子代大鼠神经发育毒性的影响

The developmental neurotoxic effects in offspring of pregnant rats exposed to benzo[a]pyrene

目的 研究孕期暴露苯并（a）芘（B[a]P）对子代大鼠生理发育、早期行为发育、对环境的适应能力及学习记忆能力的影响.方法 SD孕鼠随机分为未处理对照组（每日正常饲养）、溶剂对照组（橄榄油）、低剂量组（25mg/kgB[a]P）、中剂量组（50mg/kgB[a]P）、高剂量组（100mg/kg B[a]P）,于妊娠第17天开始,每天1次腹腔注射染毒,连续3 d,待其自然分娩.仔鼠出生后第1、4、7、14、28天称量体重,检测仔鼠生理发育、运动反射及感觉功能等发育指标,用Morris水迷宫试验和旷场试验分别评价仔鼠的学习记忆能力和对新异环境的适应能力.结果 与未处理对照组[（3.3±0.5）d]和溶剂对照组[（3.4±0.6）d]比较,中、高剂量组仔鼠张耳时间[（4.1±0.4）、（5.0±0.4）d]延长,差异有统计学意义（P＜0.01）.与未处理对照组（36、1%）相比,第4天高剂量组平面翻正试验达标率（6.5%）明显降低,与未处理对照组和溶剂对照组（81.3%、79.3%）相比,第7天时高剂量组仔鼠平面翻正试验达标率（50.0%）明显降低,差异有统计学意义（P＜0.05）.与未处理对照组比较,第12、14天时各染毒组仔鼠前肢悬挂时间均减少;与溶剂对照组比较,第14天时高剂量组仔鼠前肢悬挂时间减少,差异有统计学意义（P＜0.01）.与未处理对照组（94.3%）相比,第12天时高剂量组仔鼠嗅觉定向试验达标率（61.9%）明显降低,差异有统计学意义（P＜0.05）.Morris水迷宫试验结果表明,与未处理对照组和溶剂对照组比较,各剂量组仔鼠逃避潜伏期明显增加,高剂量组在目标象限停留时间和穿越平台次数减少,差异均有统计学意义（P＜0.01）.旷场实验结果表明,与未处理对照组[（2.40±0.89）、（82.2±15.9）、（17.4±3.9）s]比较,中、高剂量组仔鼠中央格停留时间[（9.67±1.53）、（12.80±3.77）s]明显延长,跨格次数（51.3±8.7、49.4±20.0）明显减少,高剂量组直立次数（8.0±2.6）明显减少,差异均有统计学意义（P＜0.05）;与溶剂对照组相比,各剂量组跨格次数明显减少,差异均有统计学意义（P＜0.01,P＜0.05）.结论 孕期暴露B[a]P对仔鼠的生理发育、早期行为发育产生一定的抑制作用,并对仔鼠大脑学习记忆能力及其对新异环境的适应能力有一定影响.

Objective To study the effects of prenatal exposure to benzo[a]pyrene （B[a]P） on the physical development, early behavioral development, the adaptability to new environment and the learning and memory ability of rat offspring. Methods Pregnant rats were randomly divided into five groups： control group,olive oil group, 3 exposure groups （25, 50 and 100 mg/kg B [a]P）. The rats were exposed to B [a]P） by intraperitoneal injection on the 17th-19th days during gestation. The offspring were weighed on postnatal days （PND）1, PND 4, PND 7 and PND 28, the indices of physical development, reflective ability and sensory function were detected for offspring, the Morris water maze and Open-field tests were used to measure the ability of learning and memory and the adaptability to new environment of offspring. Results The time of ear opening in middle and high-dose groups[（4. 1 ±0.4）,（5.0±0.4） d] was posterior to that in untreated and solvent groups[（3.3±0.5）,（3.4±0.6） d]（P＜0.01）.The attainment rate （6.5%） of the surface righting reflex test in highdose group on the 4th day was significantly lower than that （36.1%） in untreated group, the attainment rate（50.0%） in high-dose group on PND7 was significantly lower than those （81.3% and 79.3%） in untreated group and solvent group （P＜0.05）. Compared to the untreated group, the time of forelimb hanging test in all exposure groups on PND12 and PND14 significantly decreased; compared to the solvent group the time of forelimb hanging test decreased in high-dose group on the 14th day significantly decreased （P＜0.01）. The attainment rate （61.9%） of olfactory discrimination in high-dose group on PND 12 was significantly lower than that （94.3%） in untreated group （P＜0.05）. The results of morris water maze test showed that the escape latency of different dose groups significantly increased, and the time of spatial probe and the times of traversing flat in high-dose group decreased significantly, as compared to the untreated and solvent groups（P＜0.01）. The results of open-field test indicated that the center retention time in middle and high-dose groups significantly prolonged, the times of crossing lattice obviously reduced, and the rearing times decreased in high-dose group,as compared to untreated（P＜0.05）.Compared to the solvent group, the times of crossing lattice in all exposure groups reduced significantly（P＜0.01 or P＜0.05）. Conclusion The prenatal exposure to B[a]P could inhibit the physical development and early behavioral development, and influence the adaptability to new environment and learning and memory ability for offspring.