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

doi:10.3969/j.issn.1006-7795.2014.01.012

首都医科大学学报 ›› 2014, Vol. 35 ›› Issue (1): 51-55.doi: 10.3969/j.issn.1006-7795.2014.01.012

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

马亚红¹, 阿布杜拉·热西提², 谢北辰², 郭鑫², 杨金奎³, 刘国庆²

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

收稿日期:2013-11-27 出版日期:2014-02-21 发布日期:2014-02-21
通讯作者: 刘国庆 E-mail:georgeliu@bjmu.edu.cn
基金资助:
国家自然科学基金（30930037）。

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

Ma Yahong¹, Abudula·Rexiti², Xie Beichen², Guo Xin², Yang Jinkui³, Liu Guoqing²

1. Department of Endocrinology, Beijing Puren Hospital, Beijing 100062, China;
2. Institute of Cardiovascular Sciences, Peking University and Key Laboratory of Cardiovascular Sciences, China Administration of Education, Beijing 100091, China;
3. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China

Received:2013-11-27 Online:2014-02-21 Published:2014-02-21
Supported by:
This study was supported by the National Natural Science Foundation of China (30930037).

摘要/Abstract

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。

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

Abstract:

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.

Key words: apolipoprotein CⅢ(Apo CⅢ), transgenic mice, hypertriglyceridemia, insulin resistant, female reproduction

中图分类号:

R587.1

马亚红, 阿布杜拉·热西提, 谢北辰, 郭鑫, 杨金奎, 刘国庆. 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[J]. 首都医科大学学报, 2014, 35(1): 51-55.

Ma Yahong, Abudula·Rexiti, Xie Beichen, Guo Xin, Yang Jinkui, Liu Guoqing. Impact of severe hypertriglyceridemia in mice on female reproduction and the lipid and glucose metabolism of their offsprings[J]. Journal of Capital Medical University, 2014, 35(1): 51-55.

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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

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