| Objective:With rapid development of the society, the level of living standard has been greatly improved, which bring a huge change to people’s lifestyle, diet and working environment. The incidence of gestational diabetes mellitus(GDM) is rapidly increasing worldwide. GDM is known to result in both early perinatal complications such as macrosomia, premature, shoulder dystocia, fetal growth restriction and long-term health problems such as type 2 diabetes, obesity, hypertension, cardiovascular disease in offspring. AMP-activated proteinkinase(AMPK) plays an important role in cellular energy metabolism homoeostasis and is expressed in many tissues and cell types, including cardiomyocyte. It is cardioprotective, especially in the treatment of ischemia/reperfusion(I/R). Given its ability to act in a protective role in cardiomyocytes in a hyperglycemic environment, the aim of this study was to investigate the effects and underlying mechanisms of GDM on the post-ischemic/reperfusion(I/R) cardiac contractile function in female offspring rats. Methods:Gestational diabetic rat model was established by administrating streptozotocin(STZ, 35 mg/kg) intraperitoneally to pregnant rat on mid-term pregnancy. Rats in the control group received an injection of citrate buffer under the same conditions. The random blood glucose levels, GTT, ITT, blood pressure and heart rate of female offspring were measured before 24 weeks of age, and then the offspring rats has been subjected to ex vivo global myocardial ischemia/reperfusion by the use of Langendorff system at 24 weeks old. The signaling pathways of protein kinase B(Akt), adenine monophosphate activated protein kinase(AMPK), acetyl-coenzyme A carboxylase(ACC), Extracellular Regulated Kinase(1/2) [Erk(1/2)], Jun N-terminal kinase(JNK) in heart tissue were determined by western blot. Results:The body weight of the GDM male offspring were significantly higher than control male offspring from the age of 8 weeks(N=16, P<0.05), and it was significantly heavier in GDM female offspring than control female offspring at 23 weeks of age(N=16, P<0.05)? the heart weights and heart weight/body weight ratio was higher in the GDM male group vs. control male group(1.26±0.03 g vs.1.48±0.06 g, N=8, P<0.01 and 0.26±0.003 vs. 0.28±0.006% N=8,P<0.05, respectively), despite there were nothing changed between GDM and control female group. The phosphorylation of Akt, Erk(1/2), AMPK and ACC was markedly reduced in GDM male offspring rat hearts without I/R treatment vs. control group. The post-I/R cardiac contractile function of GDM male offspring rats was significantly compromised vs. control group(63% vs. 94%, N=4, P<0.05). Phosphorylation of AMPK and ACC was increased following a period of ischemia, but reduced following reperfusion in hearts from both control and GDM male groups. Expression, however, was significantly decreased at both time points in hearts from GDM male offspring compared to their healthy controls(N=3, P<0.05). Conclusion:This study demonstrated that GDM programed a disturbed developmental trajectory for both male and female offspring, and thus increased the risk of obesity in their later life. And it also resulted in compromised resistance to I/R stress in GDM male offspring, probably due to blunted response of cardiac AMPK activation to I/R insults. |
PDF Full Text Request