花椒毒酚抑制大鼠局灶性脑缺血/再灌注损伤后中性粒细胞浸润和脑水肿  

Inhibitory effects of xanthotoxol on neutrophil infiltration and brain edema induced by focal cerebral ischemia-reperfusion injury in rats

作　　者：何蔚[1] 陈伟伟[1] 叶和杨[1] 周钰梅[1] 黄贤华[1] 

机构地区：[1]赣南医学院药理学教研室,江西赣州341000

出　　处：《中国药理学通报》2009年第5期668-672,共5页Chinese Pharmacological Bulletin

基　　金：江西省教育厅科技计划资助项目(NoGJJ08391)

摘　　要：目的研究花椒毒酚对大鼠局灶性脑缺血/再灌注损伤后中性粒细胞浸润、细胞粘附分子表达及脑水肿的影响。方法线栓法短暂阻塞大鼠大脑中动脉制备局灶性脑缺血(2 h)再/灌注(24 h)损伤模型,缺血后1 h和12 h两次腹腔注射花椒毒酚2.5、5和10 mg.kg-1,再灌注24 h,检测大鼠神经功能行为缺陷评分、脑水肿和脑梗死范围,分光光度法测定缺血区脑组织中Na+,K+-ATPase、Ca2+-ATPase和髓过氧化物酶(MPO)的活性,免疫组织化学染色测定大脑皮层细胞间粘附分子-1(ICAM-1)和E选-择素(E-selectin)的表达。结果花椒毒酚能改善大鼠脑缺血/再灌注后神经功能行为缺陷评分,减轻脑水肿和降低脑梗死范围,增强Na+,K+-ATPase和Ca2+-ATPase活性,降低脑组织中MPO的活性,抑制ICAM-1和E-selectin表达。结论花椒毒酚对脑缺血/再灌注损伤有保护作用,其机制可能与其抑制炎症反应和减轻脑水肿有关。Aim To investigate the inhibitory effects of xanthotoxol（XT） on neutrophil infiltration and brain edema induced by focal cerebral ischemia-reperfusion injury in rats. Methods Focal cerebral ischemiareperfusion model in rat was induced by transient occlusion of the middle cerebral artery for 2 hours and followed by 24 hours of reperfusion. XT （2.5,5 and 10mg·kg^-1, ip） was administered at 1 hour and 12 hours after the onset of ischemia, respectively. After 24 hours of reperfusion, the influence of XT on neurological deficit score, brain edema and infarct size were evaluated ; the activity of Na^＋ , K^＋ -ATPase, Ca^2＋ -AT-Pase and myeloperoxidasse （MPO） in the ischemic hemisphere cortex of the middle cerebral artery area was assayed by spectrophotometry;the expression of intercellular adhesion molecule-1 （ICAM-1） and E-selectin was measured with immunohistochemistry. Resuits XT significantly reduced the neurological deficit score, brain edema and infarct size, enhanced activity of Na^＋ , K^＋-ATPase and Ca^2＋ -ATPas, suppressed the injury-induced upregulation of MPO activity and cell adhesion molecules （ ICAM-1 and E-selectin） expression in the brain tissue. Conclusion XT attenuates brain damage following focal cerebral ischemia-reperfusion in rats and its mechanism may partly be due to the inhibition of inflammation and brain edema induced by ischemia-repeffusion.

关 键 词：花椒毒酚 局灶性脑缺血/再灌注 ATP酶 髓过氧化物酶 细胞间粘附分子-1 E-选择素 

分 类 号：R-332[医药卫生] R284.1