孕期乙醇暴露所致F2代大鼠代谢综合征易感及其神经内分泌代谢编程机制

Transgenerational effects of prenatal ethanol ingestion-induced susceptibility to metabolic syndrome and the underlying mechanism in F2 rats

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.