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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: Serious hypertriglyceridemia (HTG) associated with pregnancy may induce acute pancreatitis, and adverse pregnancy outcomes are significantly increased. However, long-term effects of HTG on offspring such as glucose and lipid metabolism have not been reported. The purpose of this study was to investigate the effects of apolipoprotein CIII (Apo CIII) transgenic HTG female mice on glucose and lipid metabolism in the offspring. Methods Serious HTG female and normal female mice with Apo CIII transgenesis were mated with normal male mice to observe the fertility of severe HTG female mice. Three groups of offspring were obtained: the maternal controls were maternal control (MC) and transgenic Maternal transgenic (MT) and normal control (NC). The body mass, growth rate, triglycerides (TG), total cholesterol (TC) and glucose metabolism in the three groups were compared. Results The severe HTG caused by Apo CIII transgene had no effect on the reproductive performance of female mice. The birth weight and growth rate of the offspring of Apo CIII transgenic mice were not significantly different from the control group. MT mice Plasma TG and TC concentrations were significantly higher than those in MC and NC groups at 14 and 28 d after birth (P <0.01), and mild impaired glucose tolerance, fasting insulin (FINS) The homeostasis model assessment-insulin resistant index (HOMA-IR) was also higher than the other two groups (P <0.05). Conclusion Female Apo CIII transgenic HTG mice can be normal pregnancy, childbirth and breastfeeding. Apo CIII transgenic mice with severe HTG can cause impaired glucose tolerance, hyperinsulinemia and insulin resistance in transgenic offspring through maternal inheritance.