基于蛋白质组学技术研究氢气治疗脓毒症的分子机制

Severe sepsis is the leading cause of death in critically ill patients with no effective therapy available. Our published results prove that hydrogen gas can effectively improve the survival and organ function in mice with severe sepsis, which is closely correlated with activation of Nrf2/HO-1 pathway. However, the potential mechanism remains unclear. Recently, several differential expressed proteins in septic mice lung have been identified using the proteomics technology. Based on these research results, we will investigate the detailed mechanisms of hydrogen gas treatment for sepsis through proteomics technology. Using wild-type and Nrf2 knockout mice, we will mainly focus on Nrf2/HO-1 and other related molecules, and investigate the molecular mechanisms of hydrogen treatment in mice (severe sepsis) and in a vitro model of co-culture of vascular endothelial cells and neutrophils (a cell culture model of sepsis) through isobaric tags for relative and absolute quantitation (iTRAQ) differential protein analysis and gene regulation technologies. This study will provide a detailed mechanism for hydrogen treatment of sepsis and lay a scientific foundation for its clinical application.

重度脓毒症是危重病患者的主要死因，尚无有效治疗方法。本课题组已发表的系列研究成果证实氢气可有效治疗重度脓毒症，且与激活Nrf2/HO-1通路密切相关，但具体调控机制尚未阐明。最近，利用蛋白质组学技术已发现并鉴定多种脓毒症小鼠肺组织中差异表达蛋白。本项目拟在前期研究基础上，利用蛋白质组学技术研究氢气治疗脓毒症的相关分子机制，重点将Nrf2/HO-1及相关分子作为候选靶目标，拟利用野生型和Nrf2基因敲除型小鼠，建立离体血管内皮细胞和中性粒细胞共培养模型及在体重度脓毒症动物模型，综合运用iTRAQ差异蛋白分析技术和基因调控技术等，寻找并明确氢气治疗脓毒症的相关分子网络基础，进一步揭示氢气治疗脓毒症的具体机制，为研发脓毒症患者的救治新策略奠定科学基础。

重度脓毒症是危重病患者的主要死因，尚无有效治疗方法。本课题组已发表的系列研究成果证实氢气可有效治疗重度脓毒症，且与激活Nrf2/HO-1通路密切相关，但具体调控机制尚未阐明。最近，利用蛋白质组学技术已发现并鉴定多种脓毒症小鼠肺组织中差异表达蛋白。本项目在前期研究基础上，利用蛋白质组学技术研究氢气治疗脓毒症的相关分子机制，重点将Nrf2/HO-1及相关分子作为候选靶目标，利用野生型和Nrf2基因敲除型小鼠，建立离体血管内皮细胞和中性粒细胞共培养模型及在体重度脓毒症动物模型，综合运用iTRAQ差异蛋白分析技术和基因调控技术等，寻找并明确氢气治疗脓毒症的相关分子网络基础，进一步揭示氢气治疗脓毒症的具体机制，为研发脓毒症患者的救治新策略奠定科学基础。