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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

储利胜, 方三华, 周宇, 印媛君, 柯庆, 陈伟燕, 魏尔清1

浙江中医药大学生理学教研室，杭州 310053；浙江大学医学部药理系，杭州 310058

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30 min 后进行再灌注72 h，在再灌注30 min，2、24、48 h 时分别腹腔注射一次NDGA(5、10 mg/kg)。再灌注72 h 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3 h 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-1 mRNA 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。

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：R363.2

[Nordihydroguaiaretic acid partially inhibits inflammatory responses after focal cerebral ischemia in rats.] [Ariticle in Chinese]

CHU Li-Sheng, FANG San-Hua, ZHOU Yu, YIN Yuan-Jun, KE Qing, CHEN Wei-Yan, WEI Er-Qing

Department of Physiology, Zhejiang Chinese Medical University, Hangzhou 310053, China； Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China

Abstract

The aim of the present study is to investigate the role of nordihydroguaiaretic acid (NDGA) on inflammatory cells accumulationafter focal cerebral ischemia and the underlying mechanism. Focal cerebral ischemia was induced by 30 min of middle cerebralartery 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 IgGexudation, neutrophils and macrophages/microglia accumulation, and intercellular adhesion molecule-1 (ICAM-1) protein expressionwere 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 hafter reperfusion. The results showed that NDGA ameliorated neurological dysfunction, decreased infarct volume, and inhibitedendogenous IgG exudation, neutrophils infiltration, ICAM-1 mRNA and protein expression 72 h after reperfusion. Moreover, NDGAreduced 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 focalcerebral ischemia via inhibiting 5-LOX activation.

Key words: nordihydroguaiaretic acid; brain ischemia; neutrophils; macrophages; microglia; 5-lipoxygenase

收稿日期：2009-12-07　　录用日期：2010-01-20

通讯作者：储利胜　　E-mail: chulisheng@21cn.com

引用本文：

储利胜, 方三华, 周宇, 印媛君, 柯庆, 陈伟燕, 魏尔清1. 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[J]. 生理学报 2010; 62 (2): 101-108.

CHU Li-Sheng, FANG San-Hua, ZHOU Yu, YIN Yuan-Jun, KE Qing, CHEN Wei-Yan, WEI Er-Qing. [Nordihydroguaiaretic acid partially inhibits inflammatory responses after focal cerebral ischemia in rats.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (2): 101-108 (in Chinese with English abstract).