β-石竹烯对脑缺血再灌注大鼠血脑屏障的保护作用  

Protective effects of β- caryophyllene on blood- brain barrier of rats following cerebral ischemia and reperfusion injury

作　　者：李然然[1] 董志[1] 曹光秀[1] 刘洁[1] 

机构地区：[1]重庆医科大学药学院生化与分子药理研究室,重庆400016

出　　处：《中国新药与临床杂志》2016年第3期204-209,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金面上项目(81173066);国家科技重大专项重大新药创制(2010ZX09401-306-1-1);重庆市自然科学基金重点项目(CSTC2009BA5086)

摘　　要：目的观察β-石竹烯在局灶性脑缺血再灌注损伤模型中对大鼠血脑屏障的影响。方法采用中动脉栓塞法建立大鼠局灶性脑缺血再灌注损伤模型,分别设假手术组、模型组、β-石竹烯组(34、102、306 mg·kg^(-1))和尼莫地平(4 mg·kg^(-1))组。2,3,7-三苯基氯化四氮唑(TTC)染色法测定大鼠的脑梗死体积,伊文思蓝法观察大鼠血脑屏障通透性的改变。免疫组化法观察缺血核心区皮质水通道蛋白-4(AQP-4)的阳性表达。Western blot法检测缺血核心区claudin-5水平变化和occluding的表达。结果再灌24 h后,β-石竹烯组较模型组可不同程度地改善神经缺损症状,降低神经行为学评分,减小脑梗死体积,减少缺血侧EB含量,减少AQP-4的表达,增加claudin-5和occluding的表达(P<0.05,P<0.01)。结论β-石竹烯可通过减少AQP-4的表达,上调claudin-5和occluding的表达来减轻脑缺血再灌注所导致的脑水肿,降低血脑屏障损伤。AIM To study the effects of β-caryophyllene on blood-brain barrier （BBB） of rats on the model of cerebral ischemia and reperfusion injury. METHODS Focal cerebral ischemia model in rats was established by using the endoluminal thread, and the rats were randomly divided into 6 groups： sham operation group, model group, β-caryophyllene groups （34, 102, 306 mg.kg-1） and nimodipine （4 mg.kg-1） group. The infarction volumes were measured with 2, 3, 5-triphenyl-tetrazoliumchloride （TTC） staining. The content of evans blue （EB） was measured to assess the permeability of BBB. The expression of AQP-4 was observed in the ischemic core cortex by immunohistochemisty staining. The expressions of claudin-5 and occluding protein were tested by Western bolt. RESULTS After 24 h of reperfusion, compared with the model group, β- caryophyllene improved the neural defective symptoms, reduced the neurological scores, reduced the infarction volume, decreased the content of EB in the ischemic core cortex to varying degrees （P 〈 0.05, P 〈 0.01）. In addition, β-caryophyllene could decrease the expression of AQP-4 and increase the expressions of claudin-5 and occluding compared with the model group （P 〈 0.01）. CONCLUSION β-caryophyllene can reduce the injury of BBB in rats following cerebral ischemia and reperfusion by decreasing the expression of AQP-4 and increasing the expressions of claudin-5 and occluding.

关 键 词：β-石竹烯 脑缺血 再灌注 血脑屏障 紧密连接蛋白质类 

分 类 号：R965[医药卫生—药理学]