Effects of overexpression of Nrf2 protein on placental oxidative stress and fetal cardiac function in pregnant mice with gestational diabetes mellitus / 解放军医学杂志

ABSTRACT

Objective To investigate the effects of overexpression of nuclear factor E2 related factor 2 (Nrf2) protein on placental oxidative stress and fetal cardiac function in pregnant mice with gestational diabetes mellitus. Methods Thirty-six pregnant mice were randomly divided into four groups control group, model group, pcDNA group and Nrf2 group. Pregnant mouse model of gestational diabetes was establish by intraperitoneal injection of streptozotocin (STZ); mice in each group were transfected with corresponding adenovirus or saline. RT-PCR and Western blotting were performed to detect the expression levels of Nrf2 mRNA and protein in the placenta of pregnant mice. Fasting blood glucose was measured, uterine index, total number of fetuses and abortion rate were calculated. The placental superoxide dismutase (SOD) activity, contents of reduced glutathione (GSH) and malondialdehyde (MDA) in pregnant mice were detected. HE staining was used to observe the pathological changes of liver and kidney tissue of pregnant mice. The protein expression level of Nrf2 in the heart tissue of offspring mice was detected by Western blotting. The heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular ejection fraction (LVEF) and shortening fraction (FS) of offspring mice were measured; ELISA was performed to detect the serum contents of creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI) and myoglobin (MB) of offspring mice. HE staining was used to observe the pathological changes of myocardium in offspring mice. Results Compared with the control group, the Nrf2 mRNA level, Nrf2 protein expression level, SOD activity and GSH content, as well as the HR, LVSP, LVEF and FS of the offspring mice were obviously reduced in model group and pcDNA group (P<0.05); the fasting blood glucose, abortion rate and MDA content in pregnant mice, as well as the contents of CK-MB, MB and cTnI in offspring mice increased, while the uterine index and total fetal number decreased significantly (P<0.05); while the above indicators showed no significant difference in Nrf2 group. Compared with the model group, the Nrf2 mRNA level and protein expression level, SOD activity, GSH content, as well as the HR, LVSP, LVEF and FS of offspring increased significantly in Nrf2 group; the fasting blood glucose, abortion rate and MDA content in pregnant mice, as well as the contents of CK-MB, MB and cTnI in offspring mice decreased, while the uterine index and total fetal number increased significantly (P<0.05); while the above indicators showed no significant difference in pcDNA group. In addition, HE staining results showed that Nrf2 overexpression reduced the pathological damage of liver and kidney tissues of diabetic pregnant mice and the myocardial damage of the offspring mice. Conclusion Over-expression of Nrf2 protein can alleviate placental oxidative stress in gestational diabetic pregnant mice and maintain the cardiac function of the offspring mice.