| Objective:Severe endotoxin induced organs failure, whether pulmonary or systemic in origin, is the leading cause of death in critically ill adults and children. Evidence suggests that approximately40%of patients with severe endotoxemia develop ARDS. Endotoxin has dramatic effects on the structure and function of the lungs in intact animals and isolated lung cells.Heme oxygenase-1(HO-1) is an inducible enzyme of heme and it exists in microsome of most type tissues. It belongs to antioxidases that can be easily induced by several factors such as stress,wound and hypoxemia. HO-1play an important role as antioxidant, anti-inflammatory and anti-apoptosis in cell protection. Although a lot of research showed that HO-1playing an important role in cell protection and having potential therapeutic action,the protection mechanism was not clearly. cAMP-dependent protein kinase A (cAMP-PKA) is one of the most important signaling pathways in body and play an critical role on cell multiplication,differentiation,transport,metabolism and regulation of gene expression. HO-1gene expression can be induced by PKA in rat primary hepatocyte, RAW264.7cell and C6cell. This study aims to discuss the effect of PKA on up-regulating HO-1gene expression in lipopolysaccharide-induced acute lung injury in rats with endotoxin shock and provide new ideas and methods to the protection mecanism of HO-1.Methods:Fourty-eight healthy male Sprague-Dawley rats, weighing180-220g,2.5-3.0months, were radomly divided into4groups(n=12each):normal control group (group C), acute lung injury group (group ALI), acute lung injury with H89group (group ALI+H), and inhibitor H89group (group H). In group ALI and ALI+H, LPS(10mg/kg0.5ml) was injected iv. Normal saline (0.5ml) was injected iv in group C and H at the same time.In group ALI+H and H H89(5mg/kg0.5ml) was injected s.c. at2h, normal saline (0.5ml) was injected s.c at same time in group C and ALI. The rats were then sacrificed at6h and the lungs were removed for the pathological score, caculating water ratio and testing HO-1, PKA gene expression by Western blot and RT-PCR.Results:Compared with group C, the pathological scores and water ratio were significantly increased, the expresssion of HO-1, PKA protein and HO-lmRNA was up-regulated in group ALI and ALI+H (P<0.05), no significant change was found in the parameters mentioned above in group H (P>0.05);Compared with group ALI,the pathological score and water ratio were significantly higher, the expression of HO-1, PKA and HO-1mRNA were significantly lower in group ALI+H (P<0.05).Conclusion:HO-1gene expression decreased when the PKA signaling pathway was inhibited, PKA is involved in up-regulating heme oxygenase-1gene expression in lipopolysaccharide-induced acute lung injury in rats with endotoxin shock. |
PDF Full Text Request