抗血小板溶栓素对大鼠局灶性脑缺血损伤保护作用及其机制  

Effect of Anti-Platelet Thrombolysin on Focal Cerebral Ischemia /Reperfusion Injury in Rats

作　　者：贾德武[1] 罗胜勇[2] 叶寿山 李睿[2] 贾德云 倪光玉 陈志武[3] 张国辉 戴向荣 

机构地区：[1]安徽医科大学附属医院,合肥230032 [2]安徽省医学科学研究院,合肥230061 [3]安徽医科大学药理学教研室,合肥230032 [4]兆科药业(合肥)有限公司,合肥230088

出　　处：《中国药学杂志》2014年第9期736-740,共5页Chinese Pharmaceutical Journal

基　　金：安徽省自然科学基金资助项目(1208085QH140)

摘　　要：目的探讨抗血小板溶栓素(anti-platelet thrombolysin,APT)对大鼠局灶性脑缺血再灌注损伤的保护作用及其机制。方法 SD大鼠120只,随机分为假手术组、模型组(缺血再灌注组)、阳性组(依达拉奉1 mg·kg-1)、血小板溶栓素高、中、低剂量组(0.02、0.01、0.005 mg·kg-1),每组20只。建立线栓法大鼠缺血/再灌注模型,采用行为学评价手段评测血小板溶栓素对局灶性脑缺血再灌注大鼠神经功能恢复的影响,探讨血小板溶栓素对血清中超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-Px)活性及缺血脑组织中丙二醛(MDA)和一氧化氮(NO)含量的影响,TTC染色观察抗血小板溶栓素对脑梗死面积的影响,TUNEL法原位标记海马CA1区凋亡的神经元细胞,观察其对神经元细胞凋亡的影响。结果血小板溶栓素高、中剂量组可明显改善缺血再灌注后大鼠神经功能障碍症状、减少梗死面积;高、中、低剂量组可明显抑制机体超氧化物歧化酶、谷胱甘肽过氧化酶活性的降低;高、中剂量组明显减少脑组织中丙二醛、一氧化氮的含量,抑制缺血区神经细胞的凋亡。结论血小板溶栓素具有较好的抗脑缺血再灌注损伤作用,其机制可能与抗氧化、抑制细胞凋亡有关。OBJECTIVE To investigate the protective effect of anti-platelet thrombolysin（APT） on cerebral focal isehemia reper fusion injury induced by middle cerebral artery occlusion （MCAO） in rats. METHODS One hundred and twenty SD rats were ran domly divided into six groups：sham group, model group, positive control group, APT 0. 02 , 0. 01, 0. 005 mg . kg^-l group. The rat focal isehemia-reperfusion injury model was induced by ligation of middle eerebral artery occlusion （ MCAO ）. Neurobehavioral score was evaluated in each group; SOD and GSH-Px activities in blood serum were examined, MDA and NO contents in cerebral ischemia tissue were detected ; the volume of cerebral infarction was evaluated by TTC staining; TUNEL staining was used to measure apoptosis. RESULTS Compared with model group, the APT（ 0. 02 , 0. 01 mg. kg^-1 ） group could relieve obviously the neurological deficit score and the size of infarct volume; the APT（ 0. 02 , 0. 01, 0. 005 mg. kg^-1 ） group could increase SOD and GSH-Px activities; the APT（ 0. 02 , 0. 01 mg . kg^-1 ） group could decrease the content of MDA and NO, reduced significantly the number of TUNEL-positive neurons in the hippocampal CA1 region. CONCLUSION APT has protective effect on MCAO injury in rats, which maybe related to the antioxidation and the inhibition of apoptosis.

关 键 词：抗血小板溶栓素 缺血再灌注 抗氧化 凋亡 

分 类 号：R965[医药卫生—药理学]