妊娠期过多接触糖皮质激素对子代大鼠肝脏11β-HSD1表达的印迹效应  

Imprinting effects of prenatal overexposure to glucocorticoids on 11β-hydroxysteroid dehydrogenase type 1 expression in rat offspring liver

作　　者：李召峰[1] 曲宪成[1] 万顺伦[1] 孙刚[1] 

机构地区：[1]第二军医大学基础医学部生理学教研室,上海200433

出　　处：《第二军医大学学报》2005年第1期61-64,共4页Academic Journal of Second Military Medical University

基　　金：国家重点基础研究规划 ("973"计划) 课题(G1999054000)

摘　　要：目的:探讨妊娠期过多接触糖皮质激素对子代大鼠肝脏再生糖皮质激素代谢酶11β羟基类固醇脱氢酶Ⅰ型(11βHSD1)表达的印迹效应。方法:根据大鼠发情周期进行合笼,次晨阴道涂片发现精子作为受孕0.5 d。孕鼠共8只,随机分为地塞米松(DEX)组和生理盐水(NS)组,每组4只。DEX组孕鼠整个妊娠期注射DEX 0.05 mg/(kg·d),NS组孕鼠同等条件注射NS。取DEX和NS组出生后120 d子代大鼠肝脏组织, 采用Western印迹法检测11βHSD1 蛋白,RT PCR方法检测11βHSD1 mRNA、磷酸烯醇式丙酮酸羧激酶(PEPCK) mRNA,葡萄糖氧化酶法测定血糖浓度。结果:DEX组大鼠子代出生时的体质量比NS组明显降低, 但生后120 d子代大鼠的体质量与NS组无显著性差异。生后120 d子代大鼠中DEX组雌性子代肝脏组织内11βHSD1蛋白和mRNA表达、PEPCK mRNA表达以及血糖浓度均显著高于NS组雌性子代(P<0.05),但雄性子代大鼠没有显著差异。结论:妊娠期过多接触糖皮质激素可以印迹雌性子代大鼠肝脏11βHSD1的表达增加,从而可能进一步导致PEPCK表达的增加和血糖浓度升高。这可能是妊娠期过多接触糖皮质激素印迹糖尿病发生的重要机制之一。Objective:To observe the imprinting effects of prenatal overexposure to glucocorticoids on 11β-hydroxysteroid dehydrogenase type 1(11β-HSD1) expression in the rat offspring liver. Methods: Pregnancy was determined by examining vaginal smear. Eight pregnant rats were divided into dexamethasone(DEX) group and normal saline(NS) group at random with each group containing 4 rats.DEX group was given subcutaneous injection of DEX [0.05 mg/(kg·d)] and NS group was given injection of NS.Western blot was adopted to determine 11β-HSD1 protein in the liver of the offspring at the age of 4 months;RT-PCR was used to determine 11β-HSD1 mRNA and hepatic phosphoenolpyruvate carboxykinase(PEPCK) mRNA;and glucose oxidase method was used to measure the blood glucose concentration. Results: Western blot and RT-PCR showed that prenatal overexposure to DEX increased the expression of 11β-HSD1 protein and mRNA in the liver of the female offsprings at 4 months old, but not in male offsprings.Prenatal overexposure to DEX also increased the expression of PEPCK mRNA and blood glucose level in the female offsprings at 4 months old.Conclusion:Our study suggests that prenatal overexposure to glucocorticoids throughout gestation can imprint the expression of 11β-HSD1 in rat offsprings liver, which may lead to the PEPCK overexpression and blood glucose elevation.Development of diabetes may be induced in individuals overexposed to glucocorticoids during fetal period.

关 键 词：糖皮质激素 11β羟基类固醇脱氢酶Ⅰ型 肝 妊娠 

分 类 号：R714.431[医药卫生—妇产科学]