The Role Of SIRT1 In Cardiopulmonary Injury Induced By Severe Burns

Multiple organ dysfunction is the most serious complication of after severe burns. Lung injury and myocardial injury rank the top two of organ complications after severe burns. Due to the complex damage factors caused by burn injury and various responses of the body, the pathophysiology and molecular mechanisms of organ damage after severe burns remain unclear. Up to now, there is no effective way to relieve the organ damage induced by severe burns. Therefore, the cardiopulmonary protection after severe burns has bacome one of the critical problem in burn treatment.Silent information regulator type-1(SIRT1) is a type Ⅲ deacetylase, it is widely distributed in various tissues and cells in the body, and involved in many physiological and pathological processes. Studies have shown that SIRT1 can not only reduce myocardial injury induced by hemorrhagic shock or ischemia-reperfusion injury, but also reduce lung injury induced by Lipopolysaccharide or enterotoxin B. therefore, here we hypothesize that SIRT1 could reduce cardiopulmonary injury induced by severe burns. In the current study, we aim to explore the effect of SIRT1 on cardiopulmonary injury induced by severe burns and the molecular mechanisms.Method:1. To investigate the effect of SIRT1 on myocardial injury induced by severe burns and the molecular mechanism, a rat cardiac injury model induced by 30% Total body surface area(TBSA) Ⅲ ° scalded was established. The intraperitoneal injection of resveratrol was used to increase SIRT1 expression, the differences in cardiac pathology, myocardial enzyme content in the serum,and the expression of cleaved caspase3 and inflammation factors were observed.2. To investigate the effect of SIRT1 on remote lung injury induced by severe burns and the molecular mechanisms, a rat remote lung injury model induced by 30% TBSA Ⅲ° scalded was established. The intraperitoneal injection of resveratrol was used to increase SIRT1 expression, the differences in pulmonary pathology, protein content in bronchoalveolar lavage fluid, expression of cleaved caspase3 and inflammation factors and immunofluorescence of pulmonary sections were observed.3. To investigate the effect of SIRT1 on the apoptosis of pulmonary microvascular endothelial cells(PMVECs) induced by burn serum and its molecular mechanisms, PMVECs were stimulated by burn serum to simulate the burn conditions in vitro. After interventing SIRT1 expression, difference in PMVECs apoptosis and activation of MAPK signal pathway were observed. By intervention activation of MAPK signal pathway, the effect of SIRT1 in PMVECs apoptosis induced by burn serum were also observed.Result:1. Severe scalded caused myocardial injury, and increased SIRT1 expression in cardiac tissue. Resveratrol which further increased the expression of SIRT1 remitted cardiac pathological changes, decrease LDH, CK content in the serum, relieve cardiomyocyte apoptosis and reduce the production of pro-inflammatory cytokines.2. Severe scalded caused remote lung injury, increased apoptosis of pulmonary endothelial cells and significantly upregulated SIRT1 expression in pulmonary tissue 6h post-scald. Resveratrol which further increased the expression of SIRT1 significantly remitted pulmonary pathological changes, decreased pulmonary endothelial cell permeability, reduce the production of pro-inflammatory cytokines and inhibited pulmonary endothelial cells apoptosis.3. After burn serum stimulation, the apoptosis of PMVECs was significantly increased, the expression of SIRT1 was downregulated. Resveratrol which increased the expression of SIRT1 inhibitted PMVECs apoptosis induced by burn serum; while suppression of SIRT1 expression increased PMVECs apoptosis induced by burn serum. SIRT1 inhibitted apoptosis of PMVECs induced by burn serum via p38 MAPK signaling pathway.Conclusion:SIRT1 showed a protective role in cardiopulmonary injury induced by severe burns by reducing the production of pro-inflammatory cytokines and inhibiting of cells apoptosis. SIRT1 inhibitted PMVECs apoptosis induced by burn serum via p38 MAPK signaling pathway.