丁基苯酞对低氧-复氧及细胞因子诱导的内皮细胞损伤及中性粒细胞粘附的影响  

Effects of 3 n butylphthalide on neutrophil endothelial cell adhesion and endothelial cell injury induced by anoxia/reoxygenation, interleukin 1 and tumor necrosis factor α 1

作　　者：徐皓亮[1] 冯亦璞[1] 

机构地区：[1]中国医学科学院和中国协和医科大学药物研究所,北京100050

出　　处：《中国药理学与毒理学杂志》1999年第4期281-284,共4页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金;国家科委1035 工程重大项目基金

摘　　要：用ＭＴＴ比色法及髓过氧化物酶法观察了消旋，左旋和右旋丁基苯酞（ｄｌ－，ｌ－，ｄ－ＮＢＰ）对低氧－复氧及细胞因子白介素１（ＩＬ－１），肿瘤坏死因子α（ＴＮＦ－α）引起的内皮细胞损伤及内皮细胞－中性粒细胞粘附的影响． 结果表明，低氧－复氧，ＩＬ－１ 及ＴＮＦ－α均可促进内皮－中性粒细胞的粘附，诱导内皮细胞损伤． ｄ－ＮＢＰ能显著降低低氧－复氧条件及ＩＬ－１ 所诱导的内皮－中性粒细胞粘附，且在０．１ μｍ ｏｌ·Ｌ－ １时明显抑制ＴＮＦ－α所致的内皮－中性粒细胞粘附增加． 除ｄｌ－ＮＢＰ０．０１ μｍ ｏｌ·Ｌ－ １外，ｄｌ－ＮＢＰ和ｌ－ＮＢＰ对各种原因引起的内皮－白细胞粘附增加均无影响． 另外，各型ＮＢＰ对低氧－复氧所诱导的内皮细胞损伤均有显著的改善作用，且在高浓度抑制ＩＬ－１ 所致的内皮细胞损伤；ｄｌ－ＮＢＰ能降低ＴＮＦ－α引起的内皮细胞损伤，ｌ－ＮＢＰ仅在１０ μｍ ｏｌ·Ｌ－ １水平有此作用． 结果提示ＮＢＰ可以改善低氧－复氧及ＩＬ－１，ＴＮＦ－α诱导的内皮细胞损伤，不同旋光异构体之间存在一定差异；ｄ－ＮＢＰ还可显著抑制低氧－复氧条件，ＩＬ－１ 和ＴＮＦ－α诱导的内皮－中性粒细胞粘附增加，ｌ－ＮＢＰ仅在高浓度降低ＴＮＦ－α?The effects of dl , d , l 3 n butylphthalide (NBP) on interleukin 1(IL 1), tumor necrosis factor α(TNF α), anoxia/reoxygenation induced neutrophil adhesion to endothelial cells(ECs) and EC cytotoxicity were studied. ECs from bovine aortic artery cords were isolated and cultured in vitro, and then were subjected to anoxia in an anaerobic chamber for 3 h followed by 3 h of reoxygenation, or stimulated by IL 1(200 kU·L -1 ) and TNF α (200 kU·L -1 ), respectively for 24 h. The percentage of neutrophils that adhered to the EC monolayers was measured by myeloperoxidase quantified method. Cytotoxicity of ECs was determined by the method of MTT. Along with incubation under anoxia/reoxygenation, a dramatical increase in adherence of neutrophils to ECs was observed. Similar results were observed with respect to neutrophil EC adhesion promoted by IL 1, TNF α. Hyper adherence induced by IL 1, anoxia/reoxygenation was significantly diminished following pretreatment with d NBP given 1 h before stimuli, however, the increased adhesion induced by TNF α was unchanged. Cytotoxicity studies demonstrated that anoxia/reoxygenation, IL 1 and TNF α elicited the marked EC injury, and incubation of ECs with dl ,l ,d NBP prior to these stimuli could partially blunted this injury. These findings indicate that d NBP attenuates the neutrophil EC adhesion elicited by anoxia/reoxygenation, IL 1. Furthermore, dl, l, d NBP blunt the EC injury induced by anoxia/reoxygenation, IL 1 and TNF α.

关 键 词：丁基苯酞 内皮细胞 中性粒细胞 脑缺血 

分 类 号：R972[医药卫生—药品] R743.310.5[医药卫生—药学]