虾青素对脓毒症胰岛素抵抗的作用及其机制研究

项目名称： 虾青素对脓毒症胰岛素抵抗的作用及其机制研究

项目编号： No.81201487

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 王爱民

作者单位： 中南大学

项目金额： 22万元

中文摘要： 应激性高血糖（SHG）是脓毒症患者死亡的独立危险因素；近来随机临床试验观察到其主要治疗手段强化胰岛素治疗并不能降低病死率，反而增加低血糖和其并发症的危险性；寻找胰岛素治疗的替代药物具有重要意义。虾青素（Asta）是一种安全且来源丰富的类胡萝卜素衍生物。申请者首次发现，Asta干预脓毒症大鼠可增加其血浆脂联素（APN）水平，改善胰岛素抵抗（IR）、降低SHG，保护多器官功能及提高存活率。文献显示血浆APN与胰岛素敏感性独立相关；它通过与其受体（AdipoRs）结合后相互作用影响AMPK 及PPARα 通路，改善IR。本项目拟进一步从整体动物、组织、细胞及分子水平探讨Asta是否通过对APN及AdipoRs表达的调节影响AMPK 及PPARα 通路发挥改善IR、降低SHG的作用。开展本研究，可望揭示Asta对脓毒症IR及SHG的作用及机制，为开发新的安全有效的抗脓毒症SHG药物提供实验基础。

中文关键词： 虾青素；脓毒症；胰岛素抵抗；脂联素；脂联素受体

英文摘要： Stress hyperglycemia (SHG) is an independent risk factor of sepsis mortality. Recent randomized clinical trials have found no decrease in sepsis hospital mortality under the main treatment for SHG -intensive insulin therapy (IIT), moreover, IIT could increase their risk of hypoglycaemia and its complications. It is of great importance to look for a safe and effective alternative medicine for insulin treatment. Astaxanthin (Asta), a non-toxic red carotenoids derivative, has a widespread source in natural food. We have identified, for the first time, that Asta intervention could increase the plasma level of adiponectin (APN) in rats with sepsis significantly; improve insulin resistance (IR) and reduce the morbidity of SHG, protect multiple organ function and eventually improve survival rate of septic rats. Reports in the literature show plasma APN levels are independently related to insulin sensitivity; APN interacts with its receptor (AdipoRs, AdipoR1 and AdipoR2) and then mediates AMPK and PPAR α pathways, thus improving IR. This research is aimed to discuss whether Asta intervention could improve IR and reduce SHG of septic rats and what the mechanism is. We will further discuss whether Asta could affect the expression of APN and AdipoRs, and then mediates AMPK and PPAR α pathways under the whole animal, organi

英文关键词： astaxanthin；sepsis；insulin resistance；adiponectin；adiponectin receptor