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。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：用橡胶预涂尼龙线从右侧颈外动脉插入颈内动脉，阻断大脑中动脉起始处，诱导大脑中动脉局部缺血。通过去除螺纹实现再灌注。将大鼠分为4个实验组：1)假手术对照组；2) 2小时缺血（2-0）组；3)缺血4h（4-0）组；4) 2h缺血再灌注组（2-2）。用干重法测定脑缺血半球含水量作为脑水肿指标。采用Bligh-Dyer法和薄层色谱法提取分离PAF后，采用PAF [^3H]闪烁接近测定系统测定缺血半球组织中PAF的水平。结果：假手术组、2-0组、4-0组、2-2组右脑半球含水量分别为78.45<正负>.27、79.73<正负>0.48、80.35<正负>0.30、80.93<正负>1.05%。脑含水量在缺血后显著升高，延长缺血或再灌注后进一步升高。假手术组、2-0组、4-0组和2-2组右脑组织PAF水平分别为4441<正负>46、2298<正负bbb409、2481<正负bbb679和2901<正负bbb930 ng/g干重。缺血后组织PAF水平明显降低，再灌注后组织PAF水平略有升高，但仍较低。结论：本研究中，大鼠MCA闭塞后缺血性脑水肿的进展与组织PAF水平无相关性。与先前的观点相反，组织PAF水平在长时间局灶性缺血中下降。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