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目的探讨孕期尼古丁暴露(prenatal nicotine exposure,PNE)对高脂饮食诱导下成年子代大鼠糖代谢的影响。方法尼古丁组5只Wistar孕鼠妊娠第11 d给予尼古丁皮下注射(2 mg/kg.d,分二次给予)至自然分娩,对照组5只孕鼠等容量生理盐水相同处理。在俩组孕鼠中分别每窝挑选雄鼠和雌鼠各1只,最终获得对照组和尼古丁组雄、雌性仔鼠分别各10只。仔鼠断奶后给予高脂饮食,记录每周体重及体重增长率。仔鼠出生后第20周(postnatal week 20,PW20)行口服糖耐量实验(oral glucose tolerance test,OGTT)。PW24经麻醉后处死,苏木精-伊红染色法(hematoxylin-eosin staining,HE)观察胰腺形态。结果PNE雄性和雌性仔鼠在PW1体重较对照组明显下降(P<0.01),PNE组雄性子代体重PW16显著高于对照组(P<0.05);对应的体重增长率从PW4到PW24均显著升高(P<0.05或P<0.01)。PNE组雌性子代体重与对照组无显著性差异(P>0.05),对应的体重增长率PW8到PW24显著升高(P<0.05或P<0.01)。OGTT结果表明,雌性对照组在30min出现血糖高峰值,而PNE雌性组在60min出现高峰值;糖负荷120min后PNE雄、雌性子代血胰岛素仍高于对照组。结论 PNE子代出现宫内发育迟缓(intrauterine growth retardation,IUGR),在断奶后给予高脂饮食出现明显追赶性生长,以雄性更为显著。PNE子代糖代谢相关指标发生改变,以雌性更明显。
Objective To investigate the effects of prenatal nicotine exposure (PNE) during pregnancy on glucose metabolism in adult offspring induced by high fat diet. Methods Five Wistar pregnant rats in nicotine group were injected subcutaneously with nicotine (2 mg / kg.d twice a day) to spontaneous delivery on the 11th day of gestation. Five pregnant rats in control group were treated with the same volume of saline. In each of the two groups of pregnant rats, one male and one female were selected for each litter, and the control group and the nicotine male and female offspring were given 10 rats each. Offspring gave high-fat diet after weaning, record weekly body weight and weight gain rate. The oral glucose tolerance test (OGTT) was performed on the postnatal week 20 postnatal week 20 (PW20). PW24 was sacrificed after anesthesia, and pancreas morphology was observed by hematoxylin-eosin staining (HE). Results Compared with the control group, PNE male and female offspring had significantly decreased body weight in PW1 (P <0.01). The body weight of PNE male offspring PW16 was significantly higher than that of the control group (P <0.05). The corresponding body weight gain rate was significantly increased from PW4 to PW24 (P <0.05 or P <0.01). The body weight of female offsprings in PNE group was not significantly different from that in control group (P> 0.05). The corresponding body weight growth rate was significantly increased from PW8 to PW24 (P <0.05 or P <0.01). The results of OGTT showed that the peak value of blood glucose appeared in female control group at 30min, while that in PNE female group peaked at 60min. After 120min of glucose loading, the blood insulin level of male and female offspring of PNE was still higher than that of control group. Conclusions PNE offspring have intrauterine growth retardation (IUGR). After weaning, the rats fed with high-fat diet showed significant catch-up growth, especially in males. PNE offspring glucose metabolism related indicators change, more obvious in females.