妊娠期大鼠皮下注射尼古丁对子代发育和行为的影响

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[目的]研究妊娠期大鼠皮下注射尼古丁对仔鼠发育和行为的影响。[方法]24只孕期SD大鼠随机分为对照组和1.0、2.0、4.0 mg/kg染毒组,每组6只。受孕第7天起至仔鼠出生前,给予孕鼠皮下注射0、1.0、2.0、4.0 mg/kg尼古丁生理盐水溶液1 m L,1次/d;观察仔鼠出生后生长发育的一般指标(体重、脐带脱落、耳廓展开、萌齿、睁眼)变化,测定早期神经反射、水迷宫及学习记忆能力;观察仔鼠大脑海马区神经元突触超微结构。[结果]与对照组相比,实验组仔鼠体重显著降低(P<0.05或P<0.01);耳廓张开时间,对照组(3.41±0.44)d,4.0 mg/kg组(4.43±0.47)d;萌齿时间,对照组(10.98±1.21)d,4.0 mg/kg组(13.11±1.14)d;开眼时间,对照组(13.56±1.02)d,4.0 mg/kg组(15.89±1.20)d;3项指标两组差异均有统计学意义(P<0.05)。早期神经反射,对照组仔鼠出生后第4天和第7天达标率高于各实验组;水迷宫实验,对照组仔鼠潜伏期(39.66±8.54)s,2.0 mg/kg组(55.96±8.51)s,4.0 mg/kg组(58.99±7.66)s;目标区域停留时间,对照组仔鼠(41.22±6.23)s,1.0 mg/kg组(33.25±6.98)s,2.0 mg/kg组(30.33±8.21)s,4.0 mg/kg组(22.54±8.54)s;穿越平台次数,对照组仔鼠(6.64±0.96)次,2.0 mg/kg组(4.23±1.04)次,4.0 mg/kg组(3.19±1.11)次。超微结构观察显示尼古丁对海马区神经元突触损伤作用与暴露剂量呈正相关。[结论]妊娠中晚期较大剂量尼古丁暴露影响仔鼠的生长发育,但是对仔鼠的早期神经反射及空间学习记忆能力影响相对更明显,这可能是尼古丁主要影响了神经的生长发育。 [Objective] To study the effects of subcutaneous injection of nicotine on the development and behavior of offspring rats during pregnancy. [Methods] 24 pregnant SD rats were randomly divided into control group and 1.0, 2.0 and 4.0 mg / kg exposure groups, 6 in each. Pregnant mice were injected subcutaneously with nicotine 0, 1.0, 2.0, and 4.0 mg / kg once daily for 1 m L once daily from the 7th day after conception to their offspring. The general indicators of postnatal growth and development of the pups were observed Body weight, umbilical cord loss, ear pinprick opening, molars, eyes open). The early neural reflex, water maze and learning and memory ability were measured. The synaptic ultrastructure of neurons in the hippocampus of the offspring was observed. [Results] Compared with the control group, the body weight of the offspring of the experimental group was significantly decreased (P <0.05 or P <0.01); the time of auricle opening was 3.41 ± 0.44 days in the control group and 4.43 ± 0.47 in the 4.0 mg / kg group ) d. The time of opening teeth in the control group (10.98 ± 1.21) days and 4.0 mg / kg group (13.11 ± 1.14 days), the open eye time in the control group (13.56 ± 1.02 days) and 4.0 mg / kg group (15.89 ± 1.20 days) d; There were significant differences between the three indexes in the two groups (P <0.05). In the early neural reflexes, the attainment rate of the pups in the control group was higher than that of the experimental groups on the 4th and 7th day after birth. The latency of the water maze test was 39.66 ± 8.54 s in the pups of the control group and was 55.96 ± 8.51 in the 2.0 mg / kg group ), 4.0 mg / kg group (58.99 ± 7.66) s, residence time in the target region, 41.22 ± 6.23 s in the control group, 33.25 ± 6.98 s in the 1.0 mg / kg group and 30.33 mg / kg in the control group ± 8.21) s and 4.0 mg / kg (22.54 ± 8.54) s, respectively. The number of crossing platforms was significantly higher in the control group (6.64 ± 0.96), 2.0 mg / kg group (4.23 ± 1.04) 3.19 ± 1.11) times. Ultrastructural observation showed that nicotine had a positive correlation with exposure dose in synaptic damage of neurons in hippocampus. [Conclusion] The higher dose of nicotine exposure during the second trimester of pregnancy affects the growth and development of offspring, but the effects of early neuroreception and spatial learning and memory of offspring are relatively more obvious. This may be because nicotine mainly affects the growth and development of nerves.
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