孕期尼古丁暴露所致子2代大鼠神经内分泌代谢编程改变的可遗传效应

发布时间：2019-07-06 14:58

【摘要】：目的探讨孕期尼古丁暴露所致宫内发育迟缓(IUGR)子代大鼠神经内分泌代谢编程改变的跨代遗传效应。方法 Wistar大鼠孕11 d起每天sc给予尼古丁2 mg·kg-1至分娩。子1代(F1)正常组和尼古丁组IUGR交叉配对而得子2代(F2):CC组(亲氏为正常F1)、CN组(父为正常F1,母为IUGR F1)、NC组(父为IUGR F1,母为正常F1)和NN组(亲氏为IUGR F1)。成年F2给予2周冰水游泳刺激,收集刺激前、后血样,采用放免试剂盒检测血清促肾上腺皮质激素(ACTH)水平,ELISA试剂盒检测皮质酮(CORT)水平,生化试剂盒检测葡萄糖、甘油三酯(TG)和总胆固醇(TCH)水平。结果慢性刺激前,NN组雄性子代血清CORT较CC组显著降低,为CC组的73.9%(P0.05),CN和NC组雄性子代血清TG分别升高到CC组的1.43和1.52倍(P0.05),同时CN,NC和NN组雌性子代血清TG分别升高到CC组的1.71,1.80和1.81倍(P0.05);慢性刺激后,CC组雄性子代血清CORT增加率为-1.67%,而NN组雄性子代血清CORT增加率为36.0%,NC组雄性及CN组雌性子代血糖显著升高,分别升高至各自CC对照组的1.61和1.62倍(P0.01),同时各尼古丁组雌、雄中子代血清TG增加率均较CC组显著降低(P0.05),具体表现为CN,NC和NN组雄性子代血清TG增加率分别降低至CC组的46.4%,16.7%和7.7%,而相应雌性子代血清TG增加率分别降低至CC组的20.6%,4.0%和8.4%。与CC组相比,慢性刺激前,NN组雌、雄性子代血清TCH分别下降40.5%和21.9%(P0.01);慢性刺激后,雌性子代TCH增长率升高49.7%(P0.05)。结论孕期尼古丁暴露致大鼠神经内分泌代谢编程改变具有跨代遗传效应,且具有一定的性别和亲源性差异。
[Abstract]:Objective to investigate the intergenerational genetic effect of neuroendocrine metabolic programming in (IUGR) offspring rats induced by nicotine exposure during pregnancy. Methods Wistar rats were given nicotine 2 mg kg-1 per day from 11 days of gestation until delivery. Offspring 1 generation (F1) normal group and nicotine group IUGR cross pairing to obtain the second generation (F2): CC group (parent F1), CN group (parent normal F1 group, mother IUGR F1), NC group (IUGR F1, mother normal F1) and NN group (parent F 1 is IUGR F1). Adult F2 was stimulated by ice water swimming for 2 weeks. Blood samples were collected before and after stimulation. Serum corticotropin (ACTH) levels, corticosterone (CORT) levels were measured by ELISA kit, glucose, TG (TG) and total cholesterol (TCH) levels were measured by biochemical kit. Results before chronic stimulation, the serum CORT of male offspring in NN group was significantly lower than that in CC group, which was 73.9% of that in CC group (P 0.05). The serum TG of male offspring in), CN group and NC group was 1.43 and 1.52 times higher than that in CC group (P 0.05), while the serum TG of female offspring in CN,NC and NN group was 1.71, 1.80 and 1.81 times higher than that in CC group (P 0.05). After chronic stimulation, the increase rate of serum CORT in male offspring of CC group was-1.67%, while that of male offspring of NN group was 36.0%. The blood glucose of female offspring of NC group and CN group increased significantly to 1.61 and 1.62 times of that of CC control group, respectively. at the same time, the increase rate of serum TG of female and male offspring of each nicotine group was significantly lower than that of CC group (P 0.05). The increase rate of serum TG in male offspring of NC and NN group decreased to 46.4%, 66.7% and 7.7% of that of CC group, respectively, while that of corresponding female offspring decreased to 20.6%, 4.0% and 8.4% of that of CC group, respectively. Compared with CC group, serum TCH of female and male offspring in NN group decreased by 40.5% and 21.9% respectively before chronic stimulation (P01), and TCH growth rate of female offspring increased by 49.7% (P05) after chronic stimulation. Conclusion the programming changes of neuroendocrine metabolism induced by nicotine exposure during pregnancy have intergenerational genetic effects, and there are certain gender and parental differences.
【作者单位】：武汉大学基础医学院;武汉大学发育源性疾病湖北省重点实验室;武汉大学中南医院骨科;
【基金】：国家自然科学基金(81220108026);国家自然科学基金(81430089);国家自然科学基金(81371483)~~
【分类号】：R714

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