ROLES OF PHOSPHOLIPASE A_2 IN MULTIPLE ORGAN DYSFUNCTION SYNDROME

磷脂酶 A_2 在多器官功能障碍综合征中的作用

• 批准号: 07671691
• 负责人: KOIKE Kaoru
• 金额: $ 1.47万
• 依托单位: NIPPON MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671691/
• 关键词: adult respiratory distress syndrome; multiple organ dysfunction syndrome; phospholipase A2; small intestine; ischemia; trauma; shock; infection; 出血性ショック; 敗血症性ショック; IL-6; IL-8; 好中球エラスターゼ; ヒスタミン

*1*Phospholipase A_2 (PLA_2) has been postulated as a key mediator in the development of adult respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODF) following severe trauma, hemorrhagic shock and severe infection. Our clinical research syggested that serum type II PLA_2 increased markedly in the patients of critical illness.*2*Hypoperfusion to the gut has been suggested to cause MODF following severe trauma and hemorrhagic shock. The study using RI angiography showed that disproportionate intestinal hypoperfusion persisted for a long period even after blood pressure recovered.*3*We have developed a gut ischemia-reperfusion (I/R) rat model and found that superior mesenteric artery clamp and declamp induces lung injury by a PLA_2-dependent mechanism. The subtype analysis revealed that the most part of PLA_2 existing in the ischemic gut was secretory type II.Furthermore, the pretreatment with type II PLA_2 inhibitor, S-5920, blocked gut I/R-induced lung injury.*4*These findings suggest that type II PLA_2 plays an impirtant role in the development of ARDS and MODF after severe teauma, hemorrhagic shock and severe infection. Type II PLA_2 inhibitor may become am useful drug for prevention and treatmnt of ARDS and MODS in critically injured patients.

磷脂酶A_2（PLA_2）被认为是严重创伤、失血性休克和严重感染后发生成人呼吸窘迫综合征（ARDS）和多器官功能障碍综合征（MODF）的关键介质。我们的临床研究提示，危重病患者血清Ⅱ型PLA_2明显升高。2* 肠道灌注不足被认为是导致严重创伤和失血性休克后MODF的原因。使用RI血管造影术的研究表明，即使在血压恢复后，不成比例的肠灌注不足仍持续很长一段时间。我们建立了肠缺血再灌注（I/R）大鼠模型，发现上级肠系膜上动脉阻断和解除阻断可通过PLA_2依赖性机制引起肺损伤。Ⅱ型PLA_2抑制剂S-5920可阻断肠缺血再灌注所致的肺损伤。提示Ⅱ型PLA_2在严重创伤、失血性休克和严重感染后ARDS和MODF的发生中起重要作用。Ⅱ型PLA_2抑制剂有望成为防治危重创伤患者ARDS和MODS的有效药物。

项目成果

Kaoru Koike et al: "Phospholipase A_2 in inflamed tissues and inflammatory exudotes" Progress in Surgery,Basel,Karger,Uhl W.et al, Vol24,94-103 (1997)

Kaoru Koike 等：“发炎组织和炎症渗出物中的磷脂酶 A_2”Progress inurge，Basel，Karger，Uhl W.et al，Vol24，94-103 (1997)

小池 薫 他: "出血性ショック蘇生後も腹腔内臓器への血流低下は遷延することを示唆" 日本外科感染症研究会雑誌. 9. 161-165 (1997)

Kaoru Koike 等人：“表明即使在因失血性休克而复苏后，腹腔内器官的血流量仍然减少”，日本外科传染病学会杂志 9. 161-165 (1997)。

Koike K,Moore EE,Moore FA,Franciose RJ,Fontes B,Kim FJ.: "CD11b blockade prevents lung injury despite neutrophil priming after gut ischemia/reperfusion." J.Trauma. 39. 23-28 (1995)

Koike K、Moore EE、Moore FA、Franciose RJ、Fontes B、Kim FJ.：“尽管肠道缺血/再灌注后中性粒细胞启动，但 CD11b 阻断可防止肺损伤。”

Kaoru Koike, et al: "Gut phospholipase A_2 mediates neutrophil priming and lung injury after intestinal ischemia-reperfusion." Am.J.Physiol.268. G397-G403 (1995)

Kaoru Koike 等人：“肠道磷脂酶 A_2 介导肠道缺血再灌注后中性粒细胞启动和肺损伤。”

小池 薫 他: "小腸虚血・再潅流が細菌感染に及ぼす影響" 外科と代謝・栄養. 31. 267-270 (1997)

Kaoru Koike 等人：“小肠缺血/再灌注对细菌感染的影响”《外科、代谢和营养》31. 267-270 (1997)。