摘要
目的:阐明妊娠期糖尿病(GDM)对子代心肌细胞糖脂代谢的影响,并探讨其可能的调控机制。方法:雌性昆明小鼠于妊娠中期给予腹腔注射链脲佐菌素(30 mg/kg)建立GDM模型,另设对照(control)组。分娩后F1代饲养至8周,测定随机血糖和空腹血脂等相关指标。利用CO2窒息处死F1代实验小鼠,剖开胸腔后分离心脏组织,用于后续实验。q PCR检测p300及p300/CBP相关因子(PCAF)的mRNA表达水平,q PCR及Western blot检测过氧化物酶体增殖物激活受体γ(PPAR-γ)、葡萄糖转运蛋白4(GLUT-4)及中链酰基辅酶A脱氧酶(MCAD)的mRNA和蛋白表达水平,染色质免疫共沉淀(Ch IP)结合q PCR检测p300与PPAR-γ启动子结合水平及PPAR-γ启动子区域组蛋白H3的乙酰化水平。结果:F1代小鼠血糖和总胆固醇轻度升高(P<0.05),甘油三酯、高密度及低密度脂蛋白无明显改变;心肌组织中p300、PPAR-γ、GLUT-4及MCAD表达明显降低(P<0.05),PCAF的表达两组间差异无统计学显著性;p300与PPAR-γ启动子结合水平和PPAR-γ启动子区域组蛋白H3的乙酰化水平均明显下降(P<0.05)。结论:GDM子代小鼠中p300通过介导组蛋白乙酰化修饰而下调PPAR-γ表达,可能引起心肌细胞糖脂代谢紊乱。
AIM ： To investigate the effect of gestational diabetes mellitus （GDM） on glucose-lipid metabolism in the offspring mice and the underlying mechanisms. METHODS ： Wild-type female mice were intraperitoneally injected with streptozotocin at 30 mg/kg in the second trimester of pregnancy to establish GDM model. Normal saline was used as control. FI offspring mice were fed for 8 weeks after birth. The blood glucose and lipid levels were detected randomly. The mRNA levels of p300 and p300/CBP-associated factor （PCAF） were detected by qPCR. The expression of peroxisome pro- liferator-activated receptor-^/ （PPAR-^y） , glucose transporter typer 4 （GLUT4） and medium-chain acyl-CoA dehydroge-nase （MCAD） at mRNA and protein levels was determined by qPCR and Western blot. ChIP-qPCR was employed to ana-lyze the binding status of p300 with the promoter of PPAR-y and the acetylation level of histone H3 in the promoter region of PPAR-y. RESULTS： Blood glucose and total cholesterol levels were significant increased in the offspring mice （P 〈 0.05）. The expression levels of p300, PPAR-^y, GLUT4 and MCAD were decreased compared with the control group （P 〈 0. 05） . Binding affinity of p300 with the promoter of PPAR-y was reduced （P 〈0. 05） . The level of acetylated his-tone H3 in the promoter region of PPAR-y was decreased significantly （ P 〈 0. 05 ） . CONCLUSION ： Regulation of PPAR- y expression by p300 may induce glucose-lipid metabolism disorder in the cardiomyocytes of GDM offspring mice.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2017年第12期2222-2226,共5页
Chinese Journal of Pathophysiology
关键词
妊娠期糖尿病
P300
过氧化物酶体增殖物激活受体Γ
心肌细胞
糖脂代谢紊乱
Gestational diabetes mellitus
p300
Peroxisome proliferator-activated receptor-7
Cardiomyo-cytes
Glucose-lipid metabolism disorder
