Differential role of nitric oxide pathway and heat shock protein in preconditioning and lipopolysaccharide-induced brain ischemic tolerance
Differential role of nitric oxide pathway and heat shock protein in preconditioning and lipopolysaccharide-induced brain ischemic tolerance
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DOI：
10.1016/s0014-2999(99)00893-6
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发表时间：
2000-02-11
影响因子：
5
通讯作者：
Bordet, R
中科院分区：
文献类型：
--
作者：
Puisieux, F;Deplanque, D;Bordet, R
本研究旨在探讨一氧化氮（NO）、一氧化氮合酶（NOS）和70 kDa热休克蛋白在缺血预处理和脂多糖诱导的脑缺血耐受中的作用。采用线栓法制备大鼠局灶性脑缺血模型。（1）在60 min缺血前72 h进行3 min缺血的大鼠中，（2）在给予脂多糖（0.5 mg/kg; i. p.）72 h缺血前60 min与对照组相比。缺血预处理的有益效果是不变的，尽管事先管理硝基-L-精氨酸甲酯（L-NAME），NOS抑制剂。相反，脂多糖的保护作用被L-NAME抵消。应用免疫组化技术观察到：（1）缺血预处理诱导大脑皮层70 kDa热休克蛋白表达，而脂多糖不诱导;（2）脂多糖诱导早期脑血管内皮NOS表达增加。结果提示：（1）内皮源性NO在脂多糖诱导的脑耐受中起触发作用;（2）70 kDa热休克蛋白参与了缺血预处理的脑保护作用，而脂多糖则不参与。(C)2000 Elsevier Science B. V.保留所有权利。
The purposes of this study were to investigate the role of nitric oxide (NO), nitric oxide synthase (NOS), and 70 kDa heat shock protein in brain ischemic tolerance induced by ischemic preconditioning and lipopolysaccharide. Focal cerebral ischemia was induced in rats by intraluminal middle cerebral artery occlusion. Infarct volume was significantly reduced (1) in rats subjected to 3 min ischemia 72 h prior to 60 min ischemia; (2) in rats administered lipopolysaccharide (0.5 mg/kg; i.p.) 72 h prior to 60 min ischemia compared with controls. The beneficial effect of ischemic preconditioning was unchanged despite prior administration of nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor. Conversely, the protective effect of lipopolysaccharide was nullified by L-NAME. Using immunohistochemical techniques, we observed that (1) ischemic preconditioning but not lipopolysaccharide induces the expression of 70 kDa heat shock protein in cerebral cortex and (2) lipopolysaccharide induces early increased expression of endothelial NOS in cerebral brood vessels. The results suggest that (1) endothelium-derived NO plays a role of a trigger in the brain tolerance induced by lipopolysaccharide, and (2) 70 kDa heat shock protein is involved in the protection afforded by ischemic preconditioning but not by lipopolysaccharide. (C) 2000 Elsevier Science B.V. All rights reserved.