去甲二氢愈创木酸部分抑制大鼠局灶性脑缺血后炎症反应  

Nordihydroguaiaretic acid partially inhibits inflammatory responses after focal cerebral ischemia in rats

作　　者：储利胜[1] 方三华[2] 周宇[2] 印媛君[1] 柯庆[1] 陈伟燕[1] 魏尔清[2] 

机构地区：[1]浙江中医药大学生理学教研室,杭州310053 [2]浙江大学医学部药理系,杭州310058

出　　处：《生理学报》2010年第2期101-108,共8页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China (No. 30371637);the Scientific and Technological Program of Medicine and Health of Zhejiang Province; China (No. 2004A061)

摘　　要：本实验旨在观察去甲二氢愈创木酸(nordihydroguaiaretic acid,NDGA)对大鼠局灶性脑缺血后炎症细胞聚集的作用及其机制。在大鼠大脑中动脉阻塞30min后进行再灌注72h,在再灌注30min,2、24、48h时分别腹腔注射一次NDGA(5、10mg/kg)。再灌注72h后检测脑损伤、内源性IgG渗出、中性粒细胞和巨噬细胞/小胶质细胞聚集、细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)mRNA和蛋白表达,并在再灌注3h后检测脑内5-脂氧酶(5-lipoxygenase,5-LOX)的催化产物白三烯B4(leukotriene B4,LTB4)和半胱氨酰白三烯(cysteinyl leukotrienes,CysLTs)含量。结果显示:NDGA能显著改善脑损伤,减少内源性IgG渗出、中性粒细胞浸润、ICAM-1mRNA和蛋白表达,同时降低脑内LTB4和CysLTs含量,但对巨噬细胞/小胶质细胞聚集没有影响。上述结果提示,NDGA对脑缺血亚急性期炎症反应的抑制主要表现为减少中性粒细胞浸润,机制可能与抑制5-LOX激活有关。The aim of the present study is to investigate the role of nordihydroguaiaretic acid （NDGA） on inflammatory cells accumu- lation after focal cerebral ischemia and the underlying mechanism.Focal cerebral ischemia was induced by 30 min of middle cerebral artery occlusion （MCAO） followed by 72 h of reperfusion.NDGA （5 and 10 mg/kg） was administered intraperitoneally 30 min,2,24,48 h after reperfusion,respectively.The brain injuries were observed by neurological and histological examination.Endogenous IgG exudation,neutrophils and macrophages/microglia accumulation,and intercellular adhesion molecule-1 （ICAM-1） protein expression were determined by immunohistochemistry 72 h after reperfusion.ICAM-1 mRNA was determined by RT-PCR 72 h after reperfusion.The catalysates of 5-lipoxygenase （5-LOX）,leukotriene B4 （LTB4） and cysteinyl leukotrienes （CysLTs）,were evaluated by ELISA 3 h after reperfusion.The results showed that NDGA ameliorated neurological dysfunction,decreased infarct volume,and inhibited endogenous IgG exudation,neutrophils infiltration,ICAM-1 mRNA and protein expression 72 h after reperfusion.Moreover,NDGA reduced the levels of LTB4 and CysLTs 3 h after reperfusion.However,NDGA did not reduce the accumulation of macrophages/ microglia 72 h after reperfusion.These results suggest that NDGA decreases neutrophil infiltration in the subacute phase of focal cerebral ischemia via inhibiting 5-LOX activation.

关 键 词：去甲二氢愈创木酸 脑缺血 中性粒细胞 巨噬细胞 小胶质细胞 5-脂氧酶 

分 类 号：R285[医药卫生—中药学]