| Objective: Glucocorticoid has been used to treat chronic lung disease in premature infants. However, studies accumulated so far suggest that this treatment could lead to some long-term negative effects, including cardiac abnormalities. Studies from animal experiments found that neonatal glucocorticoid treatment might cause cardiac hypertrophy, dilatation in later life, but the alteration in cardiac energy metabolism has been rarely studied. In the present study, we aim to check alterations in cardiac gene expression involved in energy metabolism in 24 weeks old rats with dexamethasone(DEX) treatment.Methods: Pups were born naturally on day 21-22 of gestation. On the day of birth(day 0) male pups were selected and randomly divided into treatment or control groups fed by "foster mothers". Pups in the treatment group were injected IP with dexamethasone(DEX) at day 1, 2 and 3(0.5, 0.3 and 0.1 μg/g body weight, respectively) after birth in the morning from 9:00 to 10:00(n=9). Controls were injected with equal volumes(10 μl/g) of saline(SAL)(n=9). Rats were weaned and separated from the foster mother at 4 weeks of age. Body weight was measured regularly and the fasting blood glucose level was measured(n=4) at 24 weeks before rats were sacrificed. Proteins were extracted from heart tissues and gene expressions of Carnitine palmitoyl transferase I B(CPT1B), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC1α), Adenosine 5’-monophosphate activated protein kinase(AMPK), Phosphorylation of adenosine 5’-monophosphate activated protein kinase(p-AMPK), Forkhead transcription factors of the O1(Fox O1), Phosphorylation of forkhead transcription factors of the O1(p-Fox O1), Pyruvate dehydrogenase kinase isoenzyme 4(PDK4) and glucose transport 4(GLUT4) were detected by Western blot. Relative gene expression were calculated by normalized with glyceraldehyde-3-phosphate dehydrogenase(GAPDH). All data were presented as mean±SD and P<0.05 was considered statistically different.Result:1 There was no difference of fasting blood glucose level between SAL and DEX group at 24 weeks of age(mmol/L)(DEX vs. SAL: 5.03±0.47 vs. 5.28±0.25,P>0.05).2 No differences were found in body weight(g), heart weight(g) and heart/body ratio(%) at 24 weeks of age between control and experiment groups(Body weight: DEX vs. SAL: 364.11±18.51 vs. 376.67±44.18, P>0.05; Heart weight: DEX vs. SAL: 1.34±0.11 vs. 1.50±0.20, P>0.05; Heart/body ratio: DEX vs. SAL: 0.37%±0.03% vs. 0.40%±0.08%, P>0.05).3 Neonatal glucocorticoids treatment reduced cardiac protein levels of PGC1α(DEX vs. SAL: 0.030±0.008 vs. 0.042±0.004, P<0.05) and GLUT4(DEX vs. SAL: 0.007±0.002 vs. 0.016±0.006, P<0.05), but increased levels of PDK4(DEX vs. SAL: 0.585±0.093 vs. 0.298±0.031, P<0.05) and CPT1B(DEX vs. SAL: 0.296±0.020 vs. 0.258±0.013, P<0.05) in 24 weeks old rats when compared with age-matched controls. Ratios of p-AMPK/AMPK(DEX vs. SAL: 0.052±0.011 vs. 0.077±0.014, P<0.05) and p-Fox O1/Fox O1(DEX vs. SAL: 0.134±0.064 vs. 0.289±0.125, P<0.05) were all found decreased in DEX-treated rats when compared with SAL animals.Conclusions:1 Compared with age-matched controls, neonatal glucocorticoid treatment caused no alterations in fasting blood glucose. No statistical differences were found in body weight, heart weight and heart/body ratio between SAL and DEX-treated animals at 24 weeks of age.2 Neonatal glucocorticoid treatment caused alterations in cardiac gene expressions involved in energy metabolism at 24 weeks of age, which exhibited decreased uptake and utilization of glucose and the increase in fatty acid uptake. |
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