孕期尼古丁暴露加重高脂饮食所致成年子代大鼠肾上腺功能紊乱及其性别差异

Prenatal nicotine exposure aggravated abnormal adrenal function and its gender differences in adult offspring rats with high-fat diet

目的通过观察孕期尼古丁暴露(PNE)所致的宫内发育迟缓(IUGR)仔鼠出生后,在高脂饮食(HFD)模型下,血中皮质酮(CORT)浓度和肾上腺甾体合成功能的变化及其性别差异,从胰岛素样生长因子^(-1)(IGF^(-1))信号通路角度探讨其发生机制。方法 PNE(2.0 m L·kg^(-1)·d^(-1))建立大鼠IUGR模型,子代断奶后给予HFD喂养直至出生后第24周。检测仔鼠血CORT含量、肾上腺甾体合成功能、IGF^(-1)信号通路及11β-HSDs/CR系统表达。结果与HFD对照组相比,PNE组♂子代血CORT浓度呈降低趋势,♀呈升高趋势;PNE组♂子代肾上腺甾体合成酶表达(如St AR、3β-HSD、P450c11)明显降低,PNE组♀子代肾上腺甾体合成酶表达(如SF^(-1)和P450c21)增加;PNE组♂子代IGF^(-1)信号通路中IGF^(-1)、IGF^(-1)R升高,PNE组♀子代IGF^(-1)信号通路各基因表达明显增加;PNE组♂子代11β-HSD2、GR表达降低,11β-HSD1/11β-HSD2比值升高,而PNE组♀子代相应的基因表达以增加为主。结论 PNE可致HFD子代大鼠肾上腺甾体合成功能异常变化,并呈现较明显的性别差异,其发生机制与尼古丁所致的肾上腺甾体合成低功能宫内编程及出生后IGF^(-1)介导的追赶性生长有关。

Aim To explore the alterations of bloodcorticosterone （CORT） level and adrenal steroidogenic function, as well as its sex specificity in intrauterine growth retardation （IUGR） rats induced by prenatal nicotine exposure （PNE） with high-fat diet （HFD） af-ter birth, and to make clear its mechanism through in-sulin-like growth factor-1 （IGF-1 ） signaling pathway. Metliods IUGR model was established by PNE （2. 0 mL·kg^-1·d^-1） , and the offspring rats wem admin-istered with HFD until postnatal week （ PW） 24 after weaning. Blood CORT concentration, adrenal steroido-genesis enzymes, expressions of IGF-1 signaling path-way and llp - HSDs/CR system were tested. Results Compared with HFD control group, the CORT concen-tration in male offsprng of PNE group represented a decrease trend, while an increase trend in female; the expressions of adrenal steroidogenesis enzymes （such as St^ VR, 3（3-HSD and P450cl1） in male offsprng de-creased ,while increased in female offsprng （ such as SF-1 and P450c21 ） ; the expressions of IGF-1 signal-ling pathway （IGF-1 and IGF-1R ） in male offspring increased, and they significantly increased in female offspring; the expression levels of 11 （3- HSD2 and GR decreased, but 11 p-HSD1/l l （3- HSD2 ratio was en-hanced in male PNE group, while in female PNE group, the corresponding gene expressions increased. Conclusions PNE could induce abnormal alterations of adrenal steroidogenic function, and exhibit apparent gender differences. The potential mechanism is related to low adrenal steroidogenesis function programming in-duced by nicotine and catch-up growth mediated by IGF-1 after birth.