妊娠糖尿病对仔鼠肺成熟的影响及吡格列酮的干预作用

Effect of Gestational Diabetes Mellitus on Lung Maturity of Pups and Intervention Effect of Pioglitazone

目的:探究妊娠糖尿病(GDM)对仔鼠肺成熟的影响及吡格列酮对肺发育的干预作用。方法:将30只SD孕鼠分为对照组、GDM组和GDM+吡格列酮组(GDM+P组),每组10只。GDM组和GDM+P组孕鼠通过腹腔注射链脲霉素(STZ,45 mg/kg)和高脂饮食饲养构建GDM孕鼠模型,GDM+P组大鼠建模后灌胃10 mg/kg的吡格列酮,对照组和GDM组孕鼠每天灌胃等体积生理盐水。分娩后,检测各组仔鼠的血糖和血浆胰岛素水平以及胎肺组织中的总磷脂量。通过苏木精伊红(HE)染色、油红O染色和透射电镜观察胎肺组织结构和形态变化。通过RT-PCR和Western blot检测胎肺组织中SP-A、SP-B、SIRT1和PPARγ的表达。结果:GDM组仔鼠的血糖水平与对照组无显著差异(P>0.05),胰岛素水平明显高于对照组(P<0.05)。与对照组相比,GDM组仔鼠胎肺组织中的总磷脂含量降低(P<0.05);胎肺组织中肺泡Ⅱ型上皮细胞(AECⅡ)数量和脂滴明显减少。与对照组相比,GDM组仔鼠胎肺组织中的SP-A、SP-B、SIRT1和PPARγ的m RNA和蛋白相对表达水平均降低(P<0.05)。吡格列酮干预显著逆转了GDM对仔鼠胰岛素、胎肺组织结构和形态变化的影响;GDM+P组仔鼠胎肺组织中的SP-A、SP-B、SIRT1和PPARγ的m RNA和蛋白相对表达水平相较GDM组均升高(P<0.05)。结论:GDM母鼠所生仔鼠存在肺发育延迟,吡格列酮干预可有效促进仔鼠的肺成熟。

Objective:To explore the effect of gestational diabetes mellitus(GDM)on lung maturity of pups and the effect of pioglitazone on lung development.Methods:30 SD pregnant rats were divided into control group,GDM group and GDM+pioglitazone group(GDM+P),10 rats in each group.GDM group and GDM+P group pregnant rats were injected with streptozotocin(STZ,45 mg/kg)and high-fat diet to construct GDM pregnant rats’model.Rats in GDM+P group was modeled with 10 mg/kg pioglitazone after intragastric administration.Pregnant rats in control group and GDM group were given an equal volume of normal saline every day.After delivery,the blood glucose and plasma insulin levels of the offspring and the total phospholipids in the fetal lung tissue in each group were measured.Fetal lung tissue structure and morphological changes were observed by hematoxylin eosin(HE)staining,oil red O staining and transmission electron microscopy.The expressions of SP-A,SP-B,SIRT1 and PPARγin fetal lung tissue were detected by RT-PCR and Western blot.Results:The blood glucose level of offspring in the GDM group was not significantly different from that of control group(P>0.05),but the insulin level of the offspring in GDM group was significantly higher than that of control group(P<0.05).Compared with control group,the total phospholipid content in the fetal lung tissue of GDM group decreased(P<0.05).In GDM group,the number of alveolar type II epithelial cells(AECII)and lipid droplets in fetal lung tissue was significantly reduced.Compared with control group,the relative expression levels of SP-A,SP-B,SIRT1,and PPARγm RNA and protein in fetal lung tissue of GDM group were reduced(P<0.05).Pioglitazone intervention significantly reversed the effects of GDM on the changes in insulin and fetal lung tissue structure and morphology of the offspring(P<0.05).Compared with GDM group,the relative m RNA and protein expression levels of SP-A,SP-B,SIRT1 and PPARγin the fetal lung tissue of the offspring in GDM+P group increased(P<0.05).Conclusion:The offspring born from GDM pregnant rats have delayed lung development,and pioglitazone intervention can effectively promote the lung maturity of offspring.