雌激素抑制脑缺血再灌注损伤后炎症反应

背景:炎性细胞因子的释放、粘附分子上调导致的白细胞浸润与脑梗死灶的形成有密切关系,哪些因素对其能产生影响已得到人们的广泛关注。目的:探讨雌激素对大鼠局灶性脑缺血再灌注损伤后炎症反应的影响。设计:随机对照实验。单位:解放军南京军区南京总医院。材料:实验在解放军南京军区南京总医院神经内科和病理科完成。成年雌性SD大鼠,制作脑缺血模型时体质量控制在280～350g。方法:大鼠分3组:对照组、卵巢切除组、雌激素治疗组(雌二醇,200μg/kg,皮下注射,每周1次,共4周)。4周后线栓法建立右侧大脑中动脉闭塞1h、2h再灌注0、1、3、6、22、70h模型。在苏木精-伊红染色缺血半球选取10个高倍视野计算脑组织内浸润的中性粒细胞均数,免疫组化检测核因子κB表达。主要观察指标:脑实质内中性粒细胞浸润程度和核因子κB表达水平。结果:①核因子-κB表达:卵巢切除组缺血1h即有表达,对照组及雌激素治疗组在缺血2h才有阳性细胞,3组均在缺血2h再灌注3h时相表达最强,后逐渐降低,卵巢切除组在再灌注70h仍有少量表达,对照组及雌激素治疗组再灌注22h后未见核因子κB阳性细胞。②在缺血2h再灌注22h时,卵巢切除组动物脑缺血区中性粒细胞浸润数量明显增多,与雌激素治疗组相比,差异有显著性差异(P=0.045)熏在缺血2h再灌注70h时,卵巢切除组仍多于对照组和雌激素治疗组,但仅和对照组的差异有显著性意义。结论:雌激素能抑制脑缺血再灌注损伤后炎症反应。

Preventing inflammatory reaction with estrogen after cerebral ischemia/reperfusion injury

BACKGROUND:Leukocytic infiltration induced by release of inflammatory cytotkines and up-regulation of adhesion molecules is closely associated with the formation of cerebral infarcted focus. The related factors have been widely studied.OBJECTIVE: To explore influence of estrogen on inflammatory reaction in rats after focal ischemia/reperfusion injury.DESIGN: Randomized controlled experiment.SETTING: Nanjing General Hospital, Nanjing Military Area Command of Chinese PLA.MATERIALS:The experiment was performed at the Department of Neurology, Department of Pathology, Nanjing General Hospital, Nanjing Military Area Command of Chinese PLA. Adult male SD rats were selected to establish cerebral ischemic models, with the body mass of 280-350 g.METHODS:The rats were assigned into 3 groups: control group,ovariectomized group and estrogen treatment group (estradiol, 200 μg/kg,subcutaneous injection, once a week for 4 weeks). Four weeks later, models with right middle cerebral artery occlusion (MCAO) for 1 hour and 2 hours as well as reperfusion for 0, 1, 3, 6, 22 and 70 hours were established with thread embolism method. Mean number of infiltrative neutrophils in brain tissue was calculated under microscope with 10 high power fields in ischemic hemisphere with hematoxylin and eosin staining. Expression of nuclear factor-κB was determined with immunohistochemical method.MAIN OUTCOME MEASURES:Infiltration of neutrophils and expression of nuclear factor-κB in brain parenchyma.RESULTS: ①Expression of nuclear factor-κB: There was expression of nuclear factor-κB in the ovariectomized group at hour 1 after ischemia.Positive cells appeared at hour 2 after ischemia in the control group and estrogen treatment group. The expression was in the peak at ischemia for 2hours and reperfusion for 3 hours in the three groups, and decreased gradually. There was slight expression at reperfusion for 70 hours in the ovariectomized group, while there was no clear factor-κB positive cell at reperfusion for 22 hours in the control group and estrogen treatment group.②Infiltrative neutrophils in cerebral ischemic region in the ovariectomized group significantly increased at ischemia for 2 hours and reperfusion for 22 hours. Compared with the estrogen treatment group, there was significant difference (P=0.045). At ischemia for 2 hours and reperfusion for 70 hours,infiltrative neutrophils in the ovariectomized group were more than those in the control group and estrogen treatment group, but there were significant differences only between ovariectomized group and control group.CONCLUSION: Estrogen can inhibit inflammatory reaction after cerebral ischemia/reperfusion injury.