[Study on adenovirus mediated antisense p38α fragment gene in suppressing apoptosis of the myocardium of neonatal rat by burn serum and hypoxia].

Objective: To investigate the relationship between the activation of p38 mitogen-activated protein kinase (p38MAPK) in the myocardium and the apoptosis in the presence of burn serum and hypoxia.

Methods: Ventricular myocardium isolated from neonatal rats were employed in this study, and they were divided into three groups as the normal control group, with the myocardium grew naturally; burn serum+ hypoxia group, in which the myocardium was stimulated by the serum collected from the rat 6 hours after burn injury involving 40% of total body surface area (TBSA), and at the same time exposed to 1%O(2), 5%CO(2), and 94%N(2); antisense blocking group, in which rats were pretreated by AD-antisense (AS) p38α, then exposed to the same conditions as burn serum+hypoxia group. The phosphorylation of p38 in the myocardium was determined by Western blotting. The level of myocardium apoptosis was determined by DNA ladder and flow cytometry.

Results: Compared with normal control group, the level of phosphorylation of p38 (gray value) was markedly increased (8.68±0.14 vs. 3.21±0.05, P<0.01) after being exposed to burn serum and hypoxia, and at the same time myocardium apoptosis was strikingly increased [(50.367±0.451)% vs. (2.063±0.111)%, P<0.01]. When the myocardium was transfected by AD-ASp38α, the phosphorylation of p38 (gray level) was decreased remarkably (5.46±0.16 vs. 8.68±0.14, P<0.01), the rate of the apoptosis was lowered remarkably [(13.200±0.121)% vs. (50.367±0.451)%, P<0.01].

Conclusion: Burn serum combined with hypoxia can induce apoptosis of the myocardium by activating p38MAPK; blockage of p38MAPK signal transduction pathway may lessen the damage of the myocardium in early period of severe burn.