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非人类灵长类动物局灶性缺血模型中的多形核白细胞行为

Polymorphonuclear leukocyte behavior in a nonhuman primate focal ischemia model.

作者信息

Ember J A, del Zoppo G J, Mori E, Thomas W S, Copeland B R, Hugli T E

机构信息

Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.

出版信息

J Cereb Blood Flow Metab. 1994 Nov;14(6):1046-54. doi: 10.1038/jcbfm.1994.137.

Abstract

There is increasing interest in the role of polymorphonuclear (PMN) leukocytes in the evolution of focal cerebral infarction. Surgical preparation of focal cerebral ischemia models may alter leukocyte reactivity and thereby make interpretation of leukocyte function following ischemia/reperfusion difficult. The effects of surgical preparation and of experimental ischemia/reperfusion on granulocyte function have been examined prospectively in a baboon model. Twenty-six adolescent male baboons underwent surgical preparation, of which 21 underwent middle cerebral artery occlusion/reperfusion. Four additional animals served as nonsurgical controls. Peripheral venous blood specimens were taken for performing assays of leukocyte function at defined intervals before and after both the surgical preparation (i.e., the overall procedure for implantation of the middle cerebral artery occlusion device) and occlusion/reperfusion. A stress-related elevation in total leukocyte number was attributed mainly to an increase in the number of circulating PMN leukocytes. Values rose from 13.9 +/- 4.9 x 10(3) to 27.8 +/- 5.8 x 10(3)/microliters, (+/- SD; n = 21) for total leukocyte number, with p < 0.001, and from 4.3 +/- 2.1 x 10(3) to 15.9 +/- 4.7 x 10(3)/microliters (n = 21) for PMN leukocytes, with p < 0.001. Surgical preparation had no effect (p > or = 0.4) on the ability of PMN leukocytes, isolated 24 h after the implantation procedure, to display polarization, O2.- production, or beta-glucuronidase release when stimulated with human C5a. A moderate decrease in the chemotactic response to C5a resolved within the 7-day postsurgery (preocclusion) period. Three-hour middle cerebral artery occlusion and 1-h reperfusion resulted in a significant reduction in C5a-induced polarization.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

多形核(PMN)白细胞在局灶性脑梗死演变过程中的作用日益受到关注。局灶性脑缺血模型的手术制备可能会改变白细胞反应性,从而使缺血/再灌注后白细胞功能的解释变得困难。在狒狒模型中,前瞻性地研究了手术制备以及实验性缺血/再灌注对粒细胞功能的影响。26只青春期雄性狒狒接受了手术制备,其中21只进行了大脑中动脉闭塞/再灌注。另外4只动物作为非手术对照。在手术制备(即大脑中动脉闭塞装置植入的整个过程)以及闭塞/再灌注之前和之后的特定时间间隔采集外周静脉血标本,用于进行白细胞功能检测。与应激相关的总白细胞数量升高主要归因于循环PMN白细胞数量的增加。总白细胞数量从13.9±4.9×10³升至27.8±5.8×10³/微升(±标准差;n = 21),p < 0.001,PMN白细胞数量从4.3±2.1×10³升至15.9±4.7×10³/微升(n = 21),p < 0.001。手术制备对植入术后24小时分离的PMN白细胞在受到人C5a刺激时表现出极化、产生O₂⁻或释放β-葡萄糖醛酸酶的能力没有影响(p≥0.4)。对C5a的趋化反应在术后7天(闭塞前)内有适度下降。大脑中动脉闭塞3小时和再灌注1小时导致C5a诱导的极化显著降低。(摘要截选至250字)

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