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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 investigate the changes of serum cholesterol, triglycerides, leptin, insulin, cortisol, high density lipoprotein and low density lipoprotein in offspring of pregnant rats with intrahepatic cholestasis of pregnancy (ICP) The expression of 7-hydroxylase (CYP7A1), peroxisome proliferator activated receptor (PPARγ) and low density lipoprotein receptor (LDLR) in the liver of 12-month-old mice. Methods Twenty pregnant SD pregnant rats were randomly divided into control group and ICP group, with 20 rats in each group. The pregnant rats in control group were subcutaneously injected with 2.0 ml · kg-1 · d-1 of vegetable oil from the 13th day of pregnancy, and ICP Groups of pregnant rats injected with 17-α-ethinyl estradiol 1.0 mg · kg-1 · d-1 subcutaneously until delivery. Twenty rabbits in each group were randomly selected from each of the low female and male mice and fed to 12 months of age. Blood samples were collected at the end of 1 month, 3 months, 6 months and 12 months after birth, respectively. Serum triglyceride and cholesterol levels were measured by enzymatic reaction method. The levels of plasma insulin and leptin were measured by specific mouse radioimmunoassay And cortisol levels. At 6 months of age, glucose tolerance test was performed to detect the changes of blood glucose levels. Liver tissues were harvested at the age of 12 months and the expression of CYP7A1, PPARγ and LDLR mRNA was detected by PCR. Results At 6 months of age, glucose tolerance test was conducted in both offspring and 6 months old offspring in ICP group. The blood glucose level of 6 months offspring in ICP group was higher than that of the control group at different time points, with significant difference (P < 0.05). The levels of CYP7A1 mRNA and LDLR mRNA in 12-month-old offspring of ICP group were significantly lower than those of control group (P <0.05). PPARγ mRNA levels were higher than the control group, the difference was statistically significant (P <0.05). With the increase of age, blood cholesterol, triglyceride, leptin, insulin, cortisol, and low density lipoprotein in female and male offspring of ICP group increased gradually. Compared with control group at 6 months and 12 months, (P <0.05). The level of high density lipoprotein (LDL) decreased. There was a significant difference between the offspring of 6 months and 12 months of age when compared with the offspring of control group (P <0.05) . Conclusion ICP has high levels of bile acid, which can cause adverse fetal intrauterine growth environment and is one of the reasons leading to metabolic diseases in children.