Department of Pathology, University of Michigan, Medical School, Ann Arbor, 48109-0532, USA.
Am J Physiol Heart Circ Physiol. 2011 Apr;300(4):H1518-29. doi: 10.1152/ajpheart.00928.2010. Epub 2011 Jan 14.
A substantial body of evidence suggests that nicotine adversely affects cerebral blood flow and the blood-brain barrier and is a risk factor for stroke. The present study investigated the effect of nicotine on cerebrovascular endothelium under basal and ischemia/reperfusion injury under in vivo condition. Nicotine (2 mg/kg sc) was administered to mice over 14 days, which resulted in plasma nicotine levels of ∼100 ng/ml, reflecting plasma concentrations in average to heavy smokers. An analysis of the phenotype of isolated brain microvessels after nicotine exposure indicated higher expression of inflammatory mediators, cytokines (IL-1β, TNF-α, and IL-18), chemokines (CCL2 and CX(3)CL1), and adhesion molecules (ICAM-1, VCAM-1, and P-selectins), and this was accompanied by enhanced leukocyte infiltration into brain during ischemia/reperfusion (P < 0.01). Nicotine had a profound effect on ischemia/reperfusion injury; i.e., increased brain infarct size (P < 0.01), worse neurological deficits, and a higher mortality rate. These experiments illuminate, for the first time, how nicotine regulates brain endothelial cell phenotype and postischemic inflammatory response at the brain-vascular interface.
大量证据表明，尼古丁会对脑血流和血脑屏障产生不良影响，是中风的一个危险因素。本研究在体内条件下，研究了尼古丁在基础状态和缺血/再灌注损伤下对脑血管内皮的影响。尼古丁（2 mg/kg sc）给小鼠给药 14 天，导致血浆尼古丁水平约为 100ng/ml，反映了平均到重度吸烟者的血浆浓度。对尼古丁暴露后分离的脑微血管表型的分析表明，炎症介质、细胞因子（IL-1β、TNF-α和 IL-18）、趋化因子（CCL2 和 CX(3)CL1）和粘附分子（ICAM-1、VCAM-1 和 P-选择素）的表达更高，并且在缺血/再灌注期间白细胞浸润到大脑中增强（P<0.01）。尼古丁对缺血/再灌注损伤有深远的影响；即增加脑梗死面积（P<0.01）、更严重的神经功能缺损和更高的死亡率。这些实验首次阐明了尼古丁如何调节血管内皮细胞表型和脑血管界面的缺血后炎症反应。
