PPARGC1A基因及其表觀遺傳修飾對孕期糖尿病大鼠糖脂代謝的影響
發(fā)布時間:2018-05-09 09:53
本文選題:表觀遺傳 + 妊娠期糖尿病; 參考:《安徽醫(yī)科大學》2014年碩士論文
【摘要】:目的:探究PPARGC1A基因在孕期糖尿病對子代代謝狀況的表觀遺傳影響中的作用。 方法:分別把SD大鼠用小劑量STZ腹腔注射和STZ加高糖高脂飲食誘導成妊娠期糖尿。℅DM)和妊娠合并糖尿病模型,得到子代大鼠后,測定其各時期體重、血糖、胰島素、甘油三酯和瘦素水平,并且對PPARGC1A基因的mRNA表達和DNA甲基化水平進行測定。 結(jié)果:妊娠合并糖尿病組和GDM組的子代大鼠出生體重分別是(6.76±0.65)g和(6.95±0.61)g,比對照組(5.69±0.37)g重,差異有統(tǒng)計學意義(均P0.05)。但是在第3周和第8周時,妊娠合并糖尿病組和GDM組子代大鼠的體重分別是3周(37.88±0.66,,38.21±0.84g)g;8周(237.33±17.17,238.67±17.32)g,與對照組(3周:37.92±0.61g,8周:239.83±15.54g)相比無統(tǒng)計學差異;妊娠合并糖尿病組和GDM組子代大鼠的不同時期體重無顯著差異。妊娠合并糖尿病組和GDM組子代大鼠的各時期血糖指標分別是3周空腹(9.27±1.29,9.18±0.87)m mol/l;3周隨機(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周隨機(14.41±1.58,14.65±1.45)m mol/l,均高于對照組(3周空腹:5.78±0.61m mol/l,隨機:8.38±0.51m mol/l;8周空腹:5.82±0.81m mol/l,隨機8.15±0.65m mol/l)水平,差異均具有統(tǒng)計學意義。妊娠合并糖尿病組和GDM組子代大鼠的空腹胰島素水平(分別是23.84±1.73m μ/l,23.24±1.37m μ/l),比對照組(27.17±1.39)m μ/l低(均P0.05),但隨機胰島素水平(分別是61.60±3.31和54.61±1.30)m μ/l卻比對照組(29.00±2.47)m μ/l要高(均P0.05),妊娠合并糖尿病組子代大鼠的瘦素水平(0.41±0.40)uμg/l比對照組(0.78±0.10)μg/l要低(P0.05),GDM組子代大鼠的瘦素水平(0.80±0.04)μ g/l與對照組無明顯差異。而妊娠合并糖尿病組和GDM子代大鼠甘油三酯水平(分別是2.78±0.19和1.81±0.39)m mol/l,比對照組(0.78±0.28)m mol/l高(P0.05),并且妊娠合并糖尿病組子鼠的甘油三酯水平更高。妊娠合并糖尿病組和GDM組子代大鼠的mRNA表達水平(分別是0.89±0.18,0.85±0.16)與對照組(1.57±0.47)相比要明顯降低(均P0.05),與此相對應(yīng)的PPARGC1A基因甲基化水平分別是(0.73±0.16,0.72±0.18,0.23±0.06),前兩組甲基化程度均比對照組高(均P0.05)。 結(jié)論:孕期糖尿病大鼠的子代代謝異常與PPARGC1A基因的高甲基化有關(guān),PPARGC1A基因的高甲基化抑制了其mRNA的表達水平,使得子代大鼠新陳代謝的調(diào)控活動受到不利影響,從而引發(fā)代謝異常的發(fā)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 鹵0.65g and 6.95 鹵0.61g, respectively, which were significantly higher than that of control group (5.69 鹵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 鹵0.66g / g 38.21 鹵0.84g / g respectively, 237.33 鹵17.17238.67 鹵17.32g / g respectively, which was not significantly different from that of control group (37.92 鹵0.61g / 8 + 239.83 鹵15.54g). There was no significant difference in body weight between gestational diabetes mellitus group and GDM group. 濡婂鍚堝茍緋栧翱鐥呯粍鍜孏DM緇勫瓙浠eぇ榧犵殑鍚勬椂鏈熻緋栨寚鏍囧垎鍒槸3鍛ㄧ┖鑵
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