Simvastatin protects hepatocytes from apoptosis by suppressing the TNF-α/caspase-3 signaling pathway in mice with burn injury.

摘要: There is increasing evidence that the liver one of main targets for organ dysfunction after thermal injury. Most patients suffering from severe burn trauma also have hepatic [1, 2]. However, it not clear whether injury induces programmed cell death in remote liver, or if an imbalance between cellular proliferation and apoptosis leads to homeostatic [3, 4]. Simvastatin, a 3-hydroxy 3-methyl-glutaryl coenzyme-A (HMG-CoA) reductase inhibitor, has clinically been shown reduce complications, including failure severely burned [5]. These effects statins be related both directly indirectly blocking HMG-CoA activity [6, 7]. Simvastatin interferes with synthesis farnesylpyrophosphate. Farnesylpyrophosphate needed many biosynthetic pathways, ubiquinone, component mitochondrial respiratory chain, post-translational lipidation proteins. pathways are all involved [8]. underlying mechanism(s) remain obscure. The primary use treat hypercholesterolemia [9]; however, accumulating data suggest exert anti-inflammatory by decreasing formation pro-inflammatory cytokines, chemokines, reactive oxygen species [10, 11]. Burn can induce significant inflammatory reactions which may trigger promote apoptosis. known suppress susceptibility burn-induced via their properties. Clinically, decrease morbidity mortality rate attributable reduction complications [12]. Therefore we hypothesize protective role on necessary evaluate statin hepatocyte apoptosis. Tumor necrosis factor-α (TNF-α), key mediator injury, leukocyte recruitment some disease conditions [13, 14]. TNF-α initiates as potent extracellular stimulator. Downstream apoptotic signaling pathway, caspase-3 plays crucial guidance cells undergo [15]. Cleavage procaspase-3 active casepase-3 expression. Furthermore, Slotta colleagues found simvastatin expression endotoxin-induced [16, 17]. It promotes affects hepatocellular TNF-α/caspase-3 pathway. In present study, hypothesized treatment reduces this anti-apoptotic reducing specifically, caspase-3. To test hypothesis, used experimental model mice were exposed then treated simvastatin.