Identification of the hepatic insulin and catecholamine signalling pathway after major trauma

创伤后的全身炎症反应导致高代谢，从而导致蛋白质的降解和分解代谢。其结果是，肌肉、皮肤、心脏、免疫系统和肝脏等重要器官的结构和功能受到损害，导致多器官衰竭和死亡。促炎介质如促炎信号转录因子、细胞因子和急性时相蛋白被认为触发和增强了这种反应，并介导了分解代谢效应，例如通过抑制生长激素-胰岛素样生长因子-I(IGF-I)-胰岛素轴。当抗炎药或抗炎性细胞因子抗体如肿瘤坏死因子、白介素1b或其受体临床失效后，人们采取不同的方法来抑制高代谢，其中之一就是应用合成生长因子。最近的研究表明，胰岛素和β受体阻滞剂(如心得安)可能是减缓高代谢的药物，因此每个细胞信号通路都是重要的。严重创伤和连续发生脓毒症后肝细胞胰岛素和儿茶酚胺的信号转录途径尚未完全确定。因此，本研究的目的是确定烧伤和脓毒症连续发作后胰岛素和儿茶酚胺信号转录途径，以及儿茶酚胺阻滞剂(如心得安)和/或胰岛素是否调节肝脏的高代谢和免疫反应，从而提供一种潜在的治疗方法。

The systemic inflammatory response after trauma leads to hypermetabolism and thus protein degradation and catabolism. As a consequence the structure and function of essential organs, such as the muscle, skin, heart, immune system and liver are compromised and contribute to multi organ failure and mortality. Pro-inflammatory mediators such as pro-inflammatory signal transcription factors, cytokines and acute-phase-proteins were thought to trigger and enhance this response and to mediate the catabolic effects, e.g. by the inhibition of the growth hormone-insulin-like growth factor-I (IGF-I)-insulin axis. After the clinical failure of anti-inflammatory agents or antibodies against pro-inflammatory cytokines such as tumor necrosis (TNF), interleukin-1b (IL-1b), or their receptors, different approaches were taken to attenuate hypermetabolism, one of which being the application of anabolic growth factors. It has been recently shown that insulin and beta blocker (e.g. propanolol) are possible agents to attenuate hypermetabolism, thus each cellular signalling pathway is of major importance. The hepatic cellular signal transcription pathway of insulin and catecholamine after major trauma and a consecutive incidence of sepsis are not entirely defined. Therefore the aim of the present study is to determine the insulin and catecholamine signal transcription pathway after a burn injury and consecutive onset of sepsis, and whether a catecholamine blocking agent (e.g. propanolol) and/or insulin modulate hepatic hypermetabolism and the immune response, thus representing a potential therapeutic approach.