[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].


CONCLUSIONS
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.
Department of Burns and Plastic Surgery, Central South University, Changsha 410008, Hunan, China.
Peng-ju
PJ
Fan
Yan
Y
Shen
Yun
Y
Huang
Jun
J
Zheng
Xiao-yuan
XY
Huang
Yue-sheng
YS
Huang
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002056:Burns / Q000150:complications / Q000378:metabolism*; D002478:Cells, Cultured; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
D048051:p38 Mitogen-Activated Protein Kinases