InsR/FoxO1信号通路对妊娠胆汁淤积症子代大鼠下丘脑中POMC表达的影响Effect of InsR/FoxO1 on the expression of POMC in the hypothalamus of intrahepatic cholestasis of pregnancy rats offspring
闫时;王晶晶;宋昭逸;时青云;
摘要(Abstract)：
目的:探讨胰岛素受体(InsR)/胰岛素调节转录因子(Fox O1)信号通路对妊娠肝内胆汁淤积症出生后6个月子代大鼠下丘脑中阿片-促黑素细胞皮质素原(POMC)表达的影响。方法:40只清洁级SD孕鼠随机分为2组,每组20只。孕第13天时,对照组孕鼠皮下注射精制植物油2.0ml/(kg·d),ICP组孕鼠皮下注射17-α-乙炔雌二醇1.0mg/(kg·d),直至孕21天。从ICP组和对照组出生子代中各随机选取雌性20只喂养至6月龄。分别在出生后1个月、3个月、6个月断尾取血。6月龄时进行糖耐量实验,检测血糖水平的变化。6月龄处死子代提取下丘脑组织,PCR法检测InsR、Fox O1及POMC mRNA表达。应用免疫组化法检测POMC在下丘脑弓状核的表达。结果:ICP组子代大鼠在出生时、1个月时体重明显低于对照组(P<0.05),6个月时体重与对照组比较无明显差异。6月龄时进行糖耐量实验,ICP 6月龄子代血糖水平在不同时间段均高于对照组子代水平,差异有统计学意义(P<0.05)。ICP组6月龄子代大鼠下丘脑中InsR、Fox O1A、POMC mRNA相对含量与对照组比较,差异有统计学意义(P<0.05)。免疫组化结果显示,ICP子代鼠下丘脑中POMC阳性细胞数明显低于对照组。结论:ICP组由于存在高胆酸水平和不良的胎儿宫内生长环境,引发子代下丘脑调控能量稳定的信号通路改变,抑制食欲细胞减少,表现为饥饿状态,导致体重增加和血糖变化明显。
关键词(KeyWords)： 胆汁淤积;下丘脑;弓状核;胰岛素受体;胰岛素调节转录因子;POMC
基金项目(Foundation): 国家自然科学基金(No:81170588)
作者(Authors): 闫时;王晶晶;宋昭逸;时青云;
DOI: 10.13283/j.cnki.xdfckjz.2015.11.001
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