妊娠期肝内胆汁淤积症孕鼠子代胆固醇代谢与胰岛素抵抗及相关基因在肝脏中的表达  

Cholesterol metabolism,insulin resistance,and expression of related genes in liver of offsprings of pregnant rats with intrahepatic cholestasis of pregnancy

作　　者：闫时 王晶晶[2] 宋昭逸 时青云[3] 

机构地区：[1]四川大学华西第二医院妇产科,四川成都610041 [2]首都医科大学动物实验中心,北京100069 [3]首都医科大学北京世纪坛医院妇产科,北京100038

出　　处：《中国妇幼保健》2016年第2期386-390,共5页Maternal and Child Health Care of China

基　　金：国家自然科学基金(81170588)

摘　　要：目的探讨妊娠期肝内胆汁淤积症(ICP)孕鼠子代在出生后不同时期血清胆固醇、甘油三酯、瘦素、胰岛素、皮质醇、高密度脂蛋白与低密度脂蛋白水平的变化及胆固醇7-羟化酶(CYP7A1)、过氧化物酶增殖物激活受体(PPARγ)、低密度脂蛋白受体(LDLR)在12月龄鼠肝脏中的表达。方法选取40只清洁级SD孕鼠,随机分为对照组和ICP组,每组20只,自孕第13天起对照组孕鼠皮下注射精制植物油2.0 ml·kg-1·d-1;ICP组孕鼠皮下注射17-α-乙炔雌二醇1.0 mg·kg-1·d-1至分娩。两组各随机选取低雌性和雄性小鼠各20只喂养至12月龄。分别在出生后1个月、3个月、6个月及12个月断尾取血,应用酶学反应方法检测血浆甘油三酯和胆固醇水平;应用特异的鼠放射免疫法测定血浆胰岛素、瘦素以及皮质醇水平;在6月龄时进行糖耐量实验,检测血糖水平的变化;在12月龄处死后提取肝脏组织,应用PCR检测CYP7A1、PPARγ、LDLR mRNA的表达。结果在子代6月龄时进行糖耐量实验,发现无论雌性和雄性鼠,ICP组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12月龄子代雌性和雄性CYP7A1 mRNA、LDLR mRNA水平均低于对照组,差异有统计学意义(P<0.05)。PPARγmRNA水平均高于对照组,差异有统计学意义(P<0.05)。随着月龄的增加,ICP组雌性和雄子代的血胆固醇、甘油三酯、瘦素、胰岛素、皮质醇、低密度脂蛋白水平逐渐升高,在6月龄和12月龄时与对照组子代相比,差异有统计学意义(P<0.05);高密度脂蛋白水平降低,在6月龄与12月龄时与对照组子代相比,差异有统计学意义(P<0.05)。结论 ICP存在高胆汁酸水平,会造成不良的胎儿宫内生长环境,是导致子代代谢疾病发生的原因之一。Objective： To explore the changes of serum cholesterol,triglycerides,leptin,insulin,corticosterone,high- density lipoprotein cholesterol（ HDL-C）,and low-density lipoprotein cholesterol（ LDL-C） levels among the offsprings of pregnant rats with intrahepatic cholestasis of pregnancy（ ICP） at different time points after birth and the expressions of cholesterol 7-alpha-hydroxylase（ CYP7A）,peroxisome proliferators activated receptor γ（ PPARγ）,and low-density lipoprotein receptor（ LDLR） in liver of offspring rats at 12 months.Methods Forty clean SD pregnant rats were selected and randomly divided into control group and ICP group,20 rats in each group; the pregnant rats in control group were injected subcutaneously with refined vegetable oil（ 2. 0 ml·kg-1·d-1） from the 13 th day; while the pregnant rats in ICP group was injected subcutaneously with 17-α-ethynylestradio（ EE）（ 1. 0 mg·kg-1·d-1） until delivery. Twenty female rats and twenty male rates were randomly selected and fed for 12 months in the two groups; tail blood specimens were obtained at 1,3,6,and 12 months after birth; enzymatic reaction method was used to detect plasma triglycerides and cholesterol levels; specific rat radioimmunoassay was used to detect the levels of plasma insulin,leptin,and corticosterone; sugar tolerance test was conducted at 6 months; the changes of blood glucose levels were detected; liver tissues were abstracted at 12 months after executing the rats; PCR was used to detect the expressions of CYP7A1,PPARγ,and LDLR mRNA. Results The levels of blood glucose at different time points among male and female offspring rats in ICP group at six months were statistically significantly higher than those in control group（ P〈0. 05）; CYP7A1 mRNA and LDLR mRNA levels among male and female offspring rats in ICP group at 12 months were statistically significantly lower than those in control group（ P〈0. 05）; PPARγ mRNA level in ICP group was statistically significantly higher than that in contro

关 键 词：胆汁淤积 妊娠 胆固醇 胰岛素抵抗 基因 

分 类 号：R714.2[医药卫生—妇产科学]