严重高三酰甘油血症对小鼠生育及其后代糖脂代谢的影响  

Impact of severe hypertriglyceridemia in mice on female reproduction and the lipid and glucose metabolism of their offsprings

作　　者：马亚红[1] 阿布杜拉.热西提 谢北辰 郭鑫[2] 杨金奎[3] 刘国庆[2] 

机构地区：[1]北京市普仁医院内分泌科,北京100062 [2]北京大学心血管研究所教育部分子心血管学重点实验室,北京100191 [3]首都医科大学附属北京同仁医院内分泌科,北京100730

出　　处：《首都医科大学学报》2014年第1期51-55,共5页Journal of Capital Medical University

基　　金：国家自然科学基金(30930037)~~

摘　　要：目的严重高三酰甘油血症(hypertriglyceridemia,HTG)伴发于妊娠可能诱发急性胰腺炎,不良妊娠结局明显增高,但关于HTG对后代的远期影响如糖脂代谢的影响未见报道。本研究旨在探讨载脂蛋白CIII(apolipoprotein CIII,Apo CIII)转基因严重HTG的雌性小鼠对后代糖脂代谢的影响。方法应用Apo CIII转基因的严重HTG雌性及正常雌性小鼠分别与正常雄性小鼠交配,观察严重HTG雌性小鼠生育能力,并得到3组后代:母系为转基因的正常(maternal control,MC)和转基因后代(maternal transgenic,MT)及正常对照组(normal control,NC)。比较了上述3组小鼠出生体质量及生长速度、血浆三酰甘油(triglycerides,TG)、总胆固醇(total cholesterol,TC)、糖代谢的差异。结果 Apo CIII转基因导致的严重HTG对雌性小鼠生育能力无影响,Apo CIII转基因的雌性小鼠所生育后代小鼠出生体质量及生长速度均与对照组差异常无统计学意义,MT组小鼠血浆TG及TC浓度于出生14及28 d均较MC及NC组显著升高(P<0.01),并出现轻度糖耐量受损,空腹胰岛素(fasting insulin,FINS)水平及稳态模型评估胰岛素抵抗指数(homeostasis model assessment-insulin resistant index,HOMA-IR)也较其他2组增高(P<0.05)。结论 Apo CIII转基因严重HTG的雌性小鼠可正常妊娠、分娩及哺乳。严重HTG的Apo CIII转基因小鼠可以通过母系遗传而导致转基因后代发生糖耐量受损,高胰岛素血症及胰岛素抵抗指数增高。Objective Severe hypertriglyceridemia （HTG） accompanied with pregnancy may induce acute pancreatitis, which could result in adverse outcomes of pregnancy. However, the effect of maternal HTG on the metabolism of lipids and glucose in offsprings remains unclear. Using apolipoprotein CIII （Apo CIII） transgenic mice with severe HTG as model system, this study sought to investigate the effects of severe HTG on the reproduction of the female mice as well as on the metabolism of lipids and glucose of the offsprings. Methods Female HTG Apo CIII transgenic and normal mice were mated with normal males to observe the effect of severe HTG on fertility and obtained three groups offsprings： maternal transgenic but normal offspring （maternal control, MC）, maternal transgenic and transgenic offspring （maternal transgenic, MT） and maternal normal and normal offspring （normal control, NC）. The three groups of mice were compared for litter size, birth weight and growth rate, plasma triglycerides （TG）, total cholesterol （TC） and differences in glucose metabolism. Results Severe HTG from Apo CIII transgene in female mice did not affect the reproduction with unchanged pregnancy and litter size. The pups from the 3 groups had similar body weight and growth rate. Influenced by Apo CIII transgene expression, the plasma TG and TC levels at 14 and 28 days were much higher in MT mice than those of MC and NC groups （ P 〈 0. 01 ）. MT mice also had mildly impaired glucose tolerance, higher fasting insulin levels and hence higher homeostasis model assessment insulin resistance index （HOMA-IR）, compared with the other two groups （P 〈 0.05）. Conclusion Severe HTG Apo CIII transgenic female mice had normal pregnancy, parturition and lactation. The maternally inherited Apo CIII severe HTG transgenic mice after weaning exhibited abnormal glucose tolerance and insulin resistance.

关 键 词：载脂蛋白CIII 转基因小鼠 高三酰甘油血症 胰岛素抵抗 雌性生殖 

分 类 号：R587.1[医药卫生—内分泌]