Koike K, Yamamoto Y, Hori Y, Ono T
Department of Emergency and Critical Care Medicine, Nippon Medical School, Tokyo, and the Discovery Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Ann Surg. 2000 Jul;232(1):90-7. doi: 10.1097/00000658-200007000-00013.
To assess the mechanistic role of group IIA phospholipase A2 (PLA2) in the process of local and distant organ injury after intestinal ischemia-reperfusion.
Intestinal ischemia-reperfusion produces lung injury by a mechanism that involves PLA2 activation, but it is unclear which isozyme is responsible for this phenomenon. Group IIA PLA2, one of the secreted forms of PLA2, is known to play a pivotal role in a variety of inflammatory reactions.
Rats underwent 45 minutes of superior mesenteric artery occlusion in the presence and absence of pretreatment with group IIA PLA2 inhibitor, S-5920/LY315920Na (20 mg/kg, subcutaneously, 30 minutes before clamping). At 2 hours of reperfusion, intestinal and lung leak was assessed by 125I-albumin tissue/blood ratio, and liver injury was estimated by serum alanine aminotransferase. PLA2 activities in tissues and sera were quantitated by phosphatidyl-glycerol/sodium cholate mixed micelle assay. PLA2 activities in tissues were also measured after in vitro preincubation with EDTA, S-5920/LY315920Na, or antirat group IIA PLA2 antibody.
Intestinal ischemia-reperfusion provoked intestinal leak, liver injury, and lung leak, whereas tissue PLA2 activity was decreased in the intestine, unchanged in the liver, and increased in the lung. Serum PLA2 activities were increased in the portal and systemic circulation during ischemia. Pretreatment with S-5920/LY315920Na eliminated PLA2 activities in all tissues and sera and only abolished lung leak. The in vitro experiment revealed that most of the intestinal and lung PLA2 activities were inhibited by EDTA, S-5920/LY315920Na, and antirat group IIA PLA2 antibody, but hepatic PLA2 activity was not.
Intestinal ischemia-reperfusion appears to produce lung injury by a mechanism that involves group IIA PLA2 activation. Intestinal ischemia-reperfusion is likely to promote intestinal and hepatic injury independent of group IIA PLA2.
评估IIA组磷脂酶A2（PLA2）在肠缺血再灌注后局部和远处器官损伤过程中的作用机制。
肠缺血再灌注通过涉及PLA2激活的机制导致肺损伤，但尚不清楚哪种同工酶负责这一现象。IIA组PLA2是PLA2的分泌形式之一，已知在多种炎症反应中起关键作用。
在有和没有用IIA组PLA2抑制剂S-5920/LY315920Na（20mg/kg，皮下注射，夹闭前30分钟）预处理的情况下，对大鼠进行45分钟的肠系膜上动脉闭塞。再灌注2小时时，通过125I-白蛋白组织/血液比值评估肠和肺渗漏，通过血清丙氨酸转氨酶评估肝损伤。通过磷脂酰甘油/胆酸钠混合胶束测定法定量组织和血清中的PLA2活性。在与乙二胺四乙酸（EDTA）、S-5920/LY315920Na或抗大鼠IIA组PLA2抗体体外预孵育后，也测量组织中的PLA2活性。
肠缺血再灌注引发肠渗漏、肝损伤和肺渗漏，而肠组织中的PLA2活性降低，肝组织中的PLA2活性不变，肺组织中的PLA2活性增加。缺血期间门静脉和体循环中的血清PLA2活性增加。用S-5920/LY315920Na预处理消除了所有组织和血清中的PLA2活性，仅消除了肺渗漏。体外实验表明，大多数肠和肺PLA2活性受到EDTA、S-5920/LY315920Na和抗大鼠IIA组PLA2抗体的抑制，但肝PLA2活性不受抑制。
肠缺血再灌注似乎通过涉及IIA组PLA2激活的机制导致肺损伤。肠缺血再灌注可能独立于IIA组PLA2促进肠和肝损伤。
