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

重大创伤后肝胰岛素和儿茶酚胺信号通路的鉴定

• 批准号: 5408475
• 负责人: Professor Dr. Marc G. Jeschke
• 金额: --
• 依托单位: Division of Plastic & Reconstructive Surgery
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2006-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5408475?language=en
• 关键词: Identification; hepatic; insulin; catecholamine; signalling

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.

创伤后的全身炎症反应导致代谢亢进，从而导致蛋白质降解和分解代谢。结果，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，并导致多器官衰竭和死亡。促炎介质如促炎信号转录因子、细胞因子和急性期蛋白被认为可以触发和增强这种反应并介导分解代谢效应，例如促炎信号转录因子、细胞因子和急性期蛋白。通过抑制生长激素-胰岛素样生长因子-I (IGF-I)-胰岛素轴。在抗炎剂或抗促炎细胞因子（如肿瘤坏死 (TNF)、白细胞介素-1b (IL-1b) 或其受体）的抗体临床失败后，人们采取了不同的方法来减轻代谢亢进，其中之一是应用合成代谢生长因子。最近的研究表明，胰岛素和β受体阻滞剂（例如普萘洛尔）可能是减轻代谢亢进的药物，因此每个细胞信号传导途径都非常重要。重大创伤和脓毒症连续发生后胰岛素和儿茶酚胺的肝细胞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，以及儿茶酚胺阻断剂（例如普萘洛尔）和/或胰岛素是否调节肝脏代谢亢进和免疫反应，从而代表一种潜在的治疗方法。