Transfection of antisense p38α gene ameliorates myocardial cell injury mediated by hypoxia and burn serum

Backgroud Myocardial damage occurs immediately following severe burns even before significant reduction in blood volume. This phenomenon is called postburn “shock heart” (“cardiac shock”), the pathogenesis of which is unclear. This study was designed to investigate the role of antisense p38α gene transfection in ameliorating hypoxia and burn serum-mediated myocardial cell injury. Methods A model of myocardial cells cultured under hypoxia and with burn serum was established. The cells were divided into control group (group C), the group cultured under hypoxia plus burn serum (group HS), and the group treated with antisense p38α gene transfection (group A-p38α) and cultured under hypoxia plus burn serum. Burn serum was collected from Wistar rats with 40% TBSA III degree burns. Hypoxia was produced using a mixed gas with 1% O2. Antisense p38α gene recombinants were constructed and expression of p38α kinase, and NF-κB subunits p50, p65 and IκBα in myocardial cells were detected by Western blot. Myocardial viability was determined by tetrazolium colorimetry (MTT). Apoptosis was detected by flow cytometry. Lactate dehydrogenase (LDH) activity in cell culture supernatants was determined. Changes in TNFα and IL-1β mRNA expression were detected by RT-PCR. Results Activation of p38α kinase, expression of NF-κB p50, NF-κB p65 and IκB protein, and TNFα and IL-1β were downregulated significantly following antisense p38α gene transfection into myocardial cells treated with hypoxia plus burn serum. Myocardial apoptosis and LDH activity in cell culture supernatants decreased markedly and myocardial viability increased significantly in the antisense p38α gene treated group. Conclusions Results demonstrated that transfection of antisense p38α gene diminishes myocardial cell injury mediated by hypoxia and burn serum, suggesting a new target for the prevention and treatment of myocardial damage after burn.