目的:通过检测孕期乙醇暴露所致 F2代的与下丘脑-垂体-肾上腺轴(HPA)相关的神经内分泌指标,探讨 F1代代谢综合征易感的可遗传效应及其神经内分泌代谢编程机制。方法健康 Wistar 雌性大鼠受孕后第11~第20天起 ig 给予乙醇4 mg·kg -1·d -1,所获 F1代仔鼠断奶后给予高脂饮食,16~20周龄合笼交配培育 F2代。F2代断奶后给予正常饮食,20周龄检测肛温;21周龄进行口服糖耐量实验检测血糖及糖耐量;24周龄麻醉处死,取血及组织检测血脂和下丘脑-垂体-肾上腺(HPA)轴活性。结果与 F2代正常对照组相比,F2代乙醇组23:00时的肛温高于正常体温(P<0.01),血皮质酮水平表达增加(P<0.05);qPCR 检测结果显示,下丘脑精氨酸加压素 mRNA 表达增加(P<0.05);血胰岛素水平降低(P <0.05),雄性糖耐量受损(P<0.05);血高密度脂蛋白-胆固醇(HDL-C)水平降低(P<0.05),而总胆固醇与 HDL-C 及血低密度脂蛋白与 HDL-C 比值升高(P<0.05,P<0.01)。结论孕期乙醇暴露所致 F2代大鼠存在代谢综合征易感,其发生机制可能与 HPA 轴相关的神经内分泌代谢编程改变有关。
OBJECTIVE To investigate the transgenerational effects of a hypothala mic-pituitary-ad-renal (HPA)axis -associated neuroendocrine metabolic progra mming alteration fro m F1 to adult second generation (F2)with prenatal ethanol ingestion.METHODS Pregnant Wistar rats were ad ministered with ethanol (4 mg·kg -1·d -1 )fro m gestational day 1 1 until delivery.F1 rats were fed a high-fat diet fro m postnatal week 4 (PW4)and were cross-mated in PW 16 -20.F2 rats were fed a standard diet fro m PW4 and rectal te mperature was measured in PW20,oral glucose tolerance test (OGTT)was con-ducted in PW21 ,blood sa mples and hypothala mus were collected in PW24 to investigate seru m lipids and HPA axis activity.RESULTS Co mparing to the F2 control group ,rectal te mperature in F2 ethanol group were higher (P〈0.01 ),sugar tolerance in F2 male group was i mpaired (P〈0.05),seru m corti-costerone and hypothala mus arginine vasopressin (AVP) mRNA were increased (P 〈0.05);seru m insulin were decreased (P〈0.05)and male rats showed i mpaired glucose tolerance (P〈0.05);seru m high-density lipoproteincholesterol (HDL-C)decrease (P 〈0.05)and total cholesterol (TCH)/HDL-C and low density lipoproteincholesterol (LDL-C)/HDL-C ratios were markedly increased (P 〈0.05,P 〈0.01 ).CONCLUSION Prenatal ethanol exposure induced metabolic syndro me has transgenerational effects,which may originate fro m the intrauterine progra mming of altered HPA axis-associated neuroen-docrine metabolis m.