PROTECTIVE EFFECTS OF HYDROGEN GAS ON MURINE POLYMICROBIAL SEPSIS VIA REDUCING OXIDATIVE STRESS AND HMGB1 RELEASE
PROTECTIVE EFFECTS OF HYDROGEN GAS ON MURINE POLYMICROBIAL SEPSIS VIA REDUCING OXIDATIVE STRESS AND HMGB1 RELEASE
复制标题
氢气通过减少氧化应激和 HMGB1 释放对鼠多微生物脓毒症的保护作用
DOI：
10.1097/shk.0b013e3181cdc4ae
复制
发表时间：
2010-07-01
期刊：
影响因子：
3.1
通讯作者：
Wang, Guolin
中科院分区：
文献类型：
--
作者：
Xie, Keliang;Yu, Yonghao;Wang, Guolin
尽管最近在抗生素治疗和重症监护方面取得了进展，但脓毒症仍然被认为是重症监护病房中最常见的死亡原因。活性氧的过度产生在脓毒症的发病机制中起重要作用。最近，有人提出，分子氢（H2）通过选择性地减少羟基自由基（·OH，最具细胞毒性的活性氧）发挥治疗性抗氧化活性，并有效地防止I/R诱导的器官损伤。因此，我们假设H2治疗对脓毒症有有益作用。在本研究中，我们发现，在盲肠结扎和穿刺（CLP）或假手术后1和6小时开始吸入H2，以浓度和时间依赖性的方式显着提高中重度CLP脓毒症小鼠的存活率。中、重度CLP组术后24 h肺组织髓过氧化物酶活性、肺湿干重比、支气管肺泡灌洗液蛋白含量、血清生化指标及脏器病理评分均明显升高，而2%H2组肺组织病理评分明显降低。此外，我们发现H2治疗对脓毒症和脓毒症相关器官损伤的有益作用与血清和组织中氧化产物水平降低、抗氧化酶活性增加以及高迁移率族蛋白1水平降低有关。ABBREVIATIONS-ALI-急性肺损伤; ALT-丙氨酸氨基转移酶; AST-天冬氨酸氨基转移酶; BAL-bronchoalveolar lavage; BUN-血尿素氮; CAT-过氧化氢酶; CLP-盲肠结扎穿刺术; Cr-肌酐; H2-氢; H2 O2-过氧化氢; HMGB 1-高迁移率族蛋白1; 8-iso-PGF 2-8-iso-PGF 2; MPO-髓过氧化物酶; ·OH-羟基自由基; ROS-活性氧; SOD-超氧化物歧化酶; W/D-湿干比
Despite recent advances in antibiotic therapy and intensive care, sepsis is still considered to be the most common cause of death in intensive care units. Excessive production of reactive oxygen species plays an important role in the pathogenesis of sepsis. Recently, it has been suggested that molecular hydrogen (H2) exerts a therapeutic antioxidant activity by selectively reducing hydroxyl radicals (•OH, the most cytotoxic reactive oxygen species) and effectively protects against organ damage induced by I/R. Therefore, we hypothesized that H2 treatment had a beneficial effect on sepsis. In the present study, we found that H2 inhalation starting at 1 and 6 h after cecal ligation and puncture (CLP) or sham operation significantly improved the survival rate of septic mice with moderate or severe CLP in a concentration- and time-dependent manner. Furthermore, moderate or severe CLP mice showed significant multiple organ damage characterized by the increases of lung myeloperoxidase activity, wet-to-dry weight ratio, protein concentration in bronchoalveolar lavage, serum biochemical parameters, and organ histopathologic scores at 24 h after CLP operation, which was significantly attenuated by 2% H2 treatment. In addition, we found that the beneficial effects of H2 treatment on sepsis and sepsis-associated organ damage were associated with the decreased levels of oxidative product, increased activities of antioxidant enzymes, and reduced levels of high-mobility group box 1 in serum and tissue. Thus, H2 inhalation may be an effective therapeutic strategy for patients with sepsis.ABBREVIATIONS-ALI-acute lung injury; ALT-alanine aminotransferase; AST-aspartate aminotransferase; BAL-bronchoalveolar lavage; BUN-blood urea nitrogen; CAT-catalase; CLP-cecal ligation and puncture; Cr-creatinine; H2-hydrogen; H2O2-hydrogen peroxide; HMGB1-high-mobility group box 1; 8-iso-PGF2&agr;-8-iso-prostaglandin F2&agr;; MPO-myeloperoxidase; •OH-hydroxyl radicals; ROS-reactive oxygen species; SOD-superoxide dismutase; W/D-wet-to-dry