当归内酯治疗大鼠局灶性脑缺血的作用机制  

Therapeutic effects and its mechanism of angelica lactone on focal cerebral ischemia in rats

作　　者：张光毅[1] 杜俊蓉[1] 旷喜[1] 姚尧[1] 刘研新[1] 汪程远[2] 钱忠明[2] 

机构地区：[1]四川大学华西药学院,四川成都610041 [2]香港理工大学应用生物与化学科技系

出　　处：《华西药学杂志》2006年第2期114-117,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的观察当归内酯对局灶性脑缺血大鼠的治疗,并探讨其作用机制。方法线栓法堵塞大脑中动脉起始处,造成大鼠局灶性脑缺血(MCAO),缺血2 h后行神经功能评分。随机将模型大鼠分为当归内酯高、低剂量组和模型组,于再灌04、h时分别灌服受试药物80、20 mg.kg-1或等体积溶媒;假手术组同时灌服等体积溶媒。再灌24 h,各组大鼠再行神经功能评分,经TTC染色法测定脑组织梗死面积,免疫组化方法检测诱导型一氧化氮合酶(iNOS)在脑组织中的表达,分光光度法测定脑组织中iNOS活性及NO含量。结果当归内酯能够显著减小MCAO所致大鼠的脑梗死面积(P<0.01),明显改善MCAO大鼠的神经症状(P<0.01),降低缺血脑组织中iNOS的表达量、酶活性以及NO水平(P<0.05或P<0.01)。结论当归内酯对大鼠局部脑缺血损伤具有明显的保护作用,其机制可能与降低缺血脑组织中iNOS表达量及其酶活性、抑制NO的细胞毒有关。OBJECTIVE To observe the therapeutic effects and its related mechanism of angelica lactone on cerebral ischemia in rats. METHODS Middle cerebral artery occlusion of rat was caused by suture. The extent of neurological deficits score was evaluated after 2 h of ischemia and the rats succeeding in cerebral ischemia were randomly allocated into 3 groups： control group, high dose and low dose groups. Angelica lactone （80, 20 mg·kg^-1, ig） was administered at 0 and 4 hour later by reperfusion, respectively. The rats of the control group and the sham - operation group were given menstruum of same volume. After 24 hour of repeffusion, the extent of neurological deficits score was reevaluated. The infarct area was measured by 2, 3,5 - triphenyltetrazolium chloride（TIC） staining technique. The content of nitric oxide （NO） and the activities of induced nitric oxide synthase （iNOS） in cerebral tissues were assayed by spectrophotometry. The iNOS expression in frontal cortex of experimental rats was investigated using immunohistochemical method by all means. RESULTS Angelica lactone distinctly decreased the infarct size and neurological deficits score （ P 〈 0.01 ）, inhibited the iNOS expression in frontal cortex of experimental rats and reduced the content of NO and the activities of iNOS in the cerebral tissues （ P 〈 0.05 or P 〈 0.01 ）. CONCLUSION Angelica lactone has protective effects on focal cerebral ischemia in rats. Its mechanism may be relevant to its inhibition of iNOS expression which could lessen the effect of NO in frontal cortex of experimental rats.

关 键 词：当归内酯 脑缺血 红四氮唑 一氧化氮合酶 免疫组化 神经功能评分 

分 类 号：R965[医药卫生—药理学]