摘要
目的探讨胰岛素和二甲双胍治疗妊娠期糖尿病（gestational diabetes mellitus，GDM）大鼠对其子代过氧化物酶体增殖物激活受体-γ辅激活因子-1A（peroxisomep roliferators activated receptor—gamma coactivator-1A，PPARGC1A）基因甲基化及糖脂代谢的影响。方法链脲佐菌素小剂量腹腔注射诱导Sprague—Dawley孕鼠GDM模型。将24只GDM孕鼠随机分为胰岛素组、二甲双胍组和对照组，每组8只。胰岛素和二甲双胍组孕鼠分别腹腔注射4U／kg胰岛素或300mg／（kg·d）二甲双胍灌胃，每3天根据血糖水平调整用量，使血糖维持于2．65～7．62mmol／L，对照组孕鼠予1ml0．9％氯化钠溶液灌胃。孕鼠自然分娩后每组取8只子鼠，检测3和8周龄时的体重和血糖。8周龄时，酶联免疫吸附法检测血清胰岛素、瘦素及甘油三酯水平，实时荧光定量一聚合酶链反应技术检测胰腺组织PPARGClAmRNA表达和DNA甲基化水平。使用单因素方差分析和LSD检验进行统计学分析。结果胰岛素组和二甲双胍组子鼠出生体重分别为（4．6±0．8）和（4．6±0．9）g，轻于对照组[（7．2±0．4）g，LSD检验，P值均为0．000]。3组子鼠3和8周龄时，体重差异均无统计学意义（F值分别为0．616和0．904，P值分别为0．550和0．420）。子鼠3和8周龄时，胰岛素组的空腹血糖分别为（5．58±1．01）和（5．98±1．47）mmol／L，二甲双胍组分别为（4．63±1．16）和（5．65±0．62）mmol／L，均低于对照组[分别为（8．83±0．73）和（10．54±0．92）mmol／L]，随机血糖变化趋势与空腹血糖一致（LSD检验，P值均〈0．05）。与对照组相比，胰岛素组和二甲双胍组子鼠8周龄时空腹胰岛素[（8．09±1．08）、（8．16±1．42）与（6．20±0．35）mmol／L]和瘦素水平均较高（（6．51±0．73）、（8．23±1．39）与（5．14±0．43）mmol／L]，而甘油三酯水平降低[（1．72±0．29）、（1．4
Objective To determine the epigenetic change in the peroxisome proliferator activated receptor-gamma coactivator-lA （PPARGC1A） gene in offspring of the gestational diabetes mellitus （ GDM ） rat model treated with insulin and metformin. Methods The GDM model was established by one intraperitoneal injection of streptozotocin on gestational day 6 in pregnant Sprague-Dawley rats. Twenty-four GDM rats were randomly assigned to insulin-treated group, metformin-treated group and non-treated group, eight in each group. GDM rats in the insulin-treated group and metformin-treated group were injected 4 U/kg insulin intraperitoneally or intragastric administrated with 300 mg/ （ kg ~ d ） metformin to maintain the glucose levels at 2.65 to 7.62 mmol/L, while rats in the non-treated group were administrated with 0.9% sodium chloride injection. Eight pups from each group were selected and their weight and blood glucose level were monitored at three and eight weeks old. Serum insulin, leptin and triglycerides were measured at eight weeks old. Pancreas PPARGCIA mRNA expression and DNA methylation were analyzed by reverse transcription-polymerase chain reaction. Analysis of variance and the LSD test were used for statistical analysis of the data, Results The birth weight of pups in the insulin-treated and metformin-treated groups were （ 4.6±0.8 ） and （ 4.6±0.9 ） g, lower than the non-treated group [ （ 7.2±0.4 ） g, LSD test, both P=0.000]. Three weeks and eight weeks later, the weight of the pups from the three groups was not statistically different （F=0.616 and 0.904, P=0.550 and 0.420 ） . Fasting blood glucose in three and eight-week-old offspring in the insulin-treated group was （5.58±1.01） and （5.98±1.47） mmol/L, andwas （4.63±1.16） and （5.65±0.62） mmol/L in the metformin-treated group, which were lower than those in the non-treated group [ （ 8.83 ±0.73 ） and （ 10.54± 0.92 ） mmol/L, respectively]. The change in random glucose was consistent with that in fasting glucos
出处
《中华围产医学杂志》
CAS
北大核心
2014年第11期755-759,共5页
Chinese Journal of Perinatal Medicine
关键词
糖尿病
妊娠
糖尿病
实验性
转录因子
甲基化
药物疗法
表观基因组学
Diabetes, gestational
Diabetes mcllitus, experimental
Transcription Factors
Methylation
Drug therapy
Epigenomics
