CAJ | 학술논문

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。
목적：통과검측잉기을순폭로소치 F2대적여하구뇌-수체-신상선축（HPA）상관적신경내분비지표，탐토 F1대대사종합정역감적가유전효응급기신경내분비대사편정궤제。방법건강 Wistar 자성대서수잉후제11～제20천기 ig 급여을순4 mg·kg -1·d -1，소획 F1대자서단내후급여고지음식，16～20주령합롱교배배육 F2대。F2대단내후급여정상음식，20주령검측항온；21주령진행구복당내량실험검측혈당급당내량；24주령마취처사，취혈급조직검측혈지화하구뇌-수체-신상선（HPA）축활성。결과여 F2대정상대조조상비，F2대을순조23：00시적항온고우정상체온（P＜0．01），혈피질동수평표체증가（P＜0．05）；qPCR 검측결과현시，하구뇌정안산가압소 mRNA 표체증가（P＜0．05）；혈이도소수평강저（P ＜0．05），웅성당내량수손（P＜0．05）；혈고밀도지단백-담고순（HDL-C）수평강저（P＜0．05），이총담고순여 HDL-C 급혈저밀도지단백여 HDL-C 비치승고（P＜0．05，P＜0．01）。결론잉기을순폭로소치 F2대대서존재대사종합정역감，기발생궤제가능여 HPA 축상관적신경내분비대사편정개변유관。
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.