PPARGC1A基因及其表观遗传修饰对孕期糖尿病大鼠糖脂代谢的影响

发布时间：2018-05-09 09:53

  本文选题：表观遗传 + 妊娠期糖尿病　； 参考：《安徽医科大学》2014年硕士论文

【摘要】：目的：探究PPARGC1A基因在孕期糖尿病对子代代谢状况的表观遗传影响中的作用。 方法：分别把SD大鼠用小剂量STZ腹腔注射和STZ加高糖高脂饮食诱导成妊娠期糖尿病（GDM)和妊娠合并糖尿病模型，得到子代大鼠后，测定其各时期体重、血糖、胰岛素、甘油三酯和瘦素水平，并且对PPARGC1A基因的mRNA表达和DNA甲基化水平进行测定。 结果：妊娠合并糖尿病组和GDM组的子代大鼠出生体重分别是（6.76±0.65）g和（6.95±0.61）g，比对照组（5.69±0.37）g重，差异有统计学意义（均P0.05）。但是在第3周和第8周时，妊娠合并糖尿病组和GDM组子代大鼠的体重分别是3周（37.88±0.66，，38.21±0.84g）g；8周（237.33±17.17，238.67±17.32）g，与对照组（3周：37.92±0.61g，8周：239.83±15.54g）相比无统计学差异；妊娠合并糖尿病组和GDM组子代大鼠的不同时期体重无显著差异。妊娠合并糖尿病组和GDM组子代大鼠的各时期血糖指标分别是3周空腹（9.27±1.29，9.18±0.87）m mol/l;3周随机（14.15±1.18，14.23±0.93)m mol/l;8周空腹（9.41±0.52，10.33±1.08）m mol/l；8周随机（14.41±1.58，14.65±1.45）m mol/l，均高于对照组（3周空腹：5.78±0.61m mol/l，随机：8.38±0.51m mol/l；8周空腹：5.82±0.81m mol/l，随机8.15±0.65m mol/l）水平，差异均具有统计学意义。妊娠合并糖尿病组和GDM组子代大鼠的空腹胰岛素水平（分别是23.84±1.73m μ/l，23.24±1.37m μ/l），比对照组（27.17±1.39）m μ/l低（均P0.05），但随机胰岛素水平（分别是61.60±3.31和54.61±1.30）m μ/l却比对照组（29.00±2.47）m μ/l要高（均P0.05），妊娠合并糖尿病组子代大鼠的瘦素水平（0.41±0.40）uμg/l比对照组（0.78±0.10）μg/l要低(P0.05)，GDM组子代大鼠的瘦素水平（0.80±0.04）μ g/l与对照组无明显差异。而妊娠合并糖尿病组和GDM子代大鼠甘油三酯水平（分别是2.78±0.19和1.81±0.39）m mol/l，比对照组（0.78±0.28）m mol/l高(P0.05)，并且妊娠合并糖尿病组子鼠的甘油三酯水平更高。妊娠合并糖尿病组和GDM组子代大鼠的mRNA表达水平（分别是0.89±0.18，0.85±0.16）与对照组（1.57±0.47）相比要明显降低（均P0.05)，与此相对应的PPARGC1A基因甲基化水平分别是（0.73±0.16,0.72±0.18,0.23±0.06），前两组甲基化程度均比对照组高（均P0.05)。 结论：孕期糖尿病大鼠的子代代谢异常与PPARGC1A基因的高甲基化有关，PPARGC1A基因的高甲基化抑制了其mRNA的表达水平，使得子代大鼠新陈代谢的调控活动受到不利影响，从而引发代谢异常的发生。
[Abstract]:Aim: to investigate the role of PPARGC1A gene in the epigenetic effects of gestational diabetes mellitus on the metabolic status of offspring. Methods: SD rats were induced into gestational diabetes mellitus (GDM) model and gestational diabetes mellitus (GDM) model by intraperitoneal injection of small dose STZ and STZ plus high glucose and high fat diet, and then the offspring rats were obtained and their body weight, blood glucose and insulin were measured. The levels of triglyceride and leptin, mRNA expression and DNA methylation of PPARGC1A gene were measured. Results: the birth weight of gestational diabetes mellitus group and GDM group were 6.76 卤0.65g and 6.95 卤0.61g, respectively, which were significantly higher than that of control group (5.69 卤0.37g). However, at the 3rd and 8th week, the body weight of the offspring of gestational diabetes mellitus group and GDM group was 37.88 卤0.66g / g 38.21 卤0.84g / g respectively, 237.33 卤17.17238.67 卤17.32g / g respectively, which was not significantly different from that of control group (37.92 卤0.61g / 8 + 239.83 卤15.54g). There was no significant difference in body weight between gestational diabetes mellitus group and GDM group. 濡婂�犲悎骞剁硸灏跨梾缁勫拰GDM缁勫瓙浠ｅぇ榧犵殑鍚勬椂鏈熻��绯栨寚鏍囧垎鍒�鏄�3鍛ㄧ┖鑵

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