Contribution of Platelet-Activating Factor (PAF) on Pathogenesis of Ischemic Cerebrovascular Disease

背景和目的：血小板活化因子(PAF)是一种磷脂介质，参与多种病理过程，如过敏、炎症、休克和创伤等。近年来，许多使用PAF拮抗剂的实验工作也提示了PAF在缺血性脑损伤中的作用。本研究探讨了大鼠局灶性脑缺血时PAF的产生与缺血性脑水肿进展的关系。方法：分离右侧颈外动脉至颈内动脉，用橡胶预涂尼龙线阻断大脑中动脉起源，造成大脑中动脉(MCA)区局灶性脑缺血，拔除线条进行再灌流。实验分为4组：1)假手术对照组，2)缺血2小时组(2-0)，3)缺血4小时组(4-0)，4)缺血2小时再灌注2小时组(2-2)。作为脑水肿的指标，…的水分含量用干重法测定缺血侧大脑半球的面积。结果：假手术组、2-0、4-0、2-2组大鼠右侧大脑半球含水量分别为78.45&lt；plus-minus&gt；0.27，79.73&lt；plus-minus&gt；0.48，80.35&lt；plus-minus&gt；0.30和80.93lt；正负1.05%。脑缺血后脑组织含水量显著增加，长时间缺血或再灌流后脑组织含水量进一步增加。而假手术组、2-0组、4-0组和2-2组大鼠右侧大脑半球组织纤溶酶原激活物水平分别为4441&lt；plus-minus&gt；346,2298&lt；plus-minus&gt；409,2481&lt；plus-minus&gt；679和930 ng/g干重。组织PAF水平在缺血时显著降低，再灌流时略有升高，但仍较低。结论：本研究未发现大鼠大脑中动脉闭塞后缺血性脑水肿的进展与组织PAF水平的关系。与先前的建议相反，组织PAF水平在长时间局灶性缺血时降低。较少

Background and Purpose : Platelet-Activating Factor (PAF) is a phospholipid mediator immplicated in a diverse range of pathological processes such as allergy, inflammation, shock and trauma. Recently, a role of PAF in ischemic brain injury also has been suggested from many experimental works using PAF antagonist. In this study we examined the correlation between PAF production and progress of ischemic brain edema in focal cerebral ischemia in rats.Methods : Focal cerebral ischemia in the are of middle cerebral artery(MCA)was induced by insertion of rubber precoated nylon thread from dissected right external carotid artery to internal carotid artery to occlude the origin of the MCA.Reperfusion was achieved by removal of the thread. The rats were divided into four experimental groups : 1) sham operated control group ; 2) 2 hours ischemia (2-0) group ; 3) 4 hours ischemia (4-0) group ; and 4) 2 hours ischemia and 2 hours reperfusion (2-2) group. As an index of brain edema, water content o … More f ischemic hemisphere was measured by dry-weight method. Tissue levels of PAF in ischemic hemisphere was measured by PAF [^3H] scintillation proximity assay system after extraction and isolation of PAF by Bligh-Dyer method and thin-layr chromatography.Results : Water contents of right cerebral hemisphere in sham, 2-0,4-0 and 2-2 groups were 78.45<plus-minus>0.27,79.73<plus-minus>0.48,80.35<plus-minus>0.30 and 80.93<plus-minus>1.05%, respectively. Cerebral water content significantly increased by ischemia, and further increased by prolonged ischemia or reperfusion. On the other hand, tissue PAF levels of right cerebral hemisphere in sham, 2-0,4-0 and 2-2 groups were 4441<plus-minus>346,2298<plus-minus>409,2481<plus-minus>679 and 2901<plus-minus>930 ng/g dry weight, respectively. Tissue PAF level significantly decreased by ischemia, and slightly increased by reperfusion but still low compareConclusions : In this study, there was no relation between progress of ischemic brain edema and tissue PAF level in MCA occlusion in rat. Contrary to previous suggestion, tissue PAF level decreased in prolonged focal ischemia. Less