咪唑酮类化合物ZLJ-6对大鼠脑缺血再灌注损伤的保护作用及其机制研究  

Protective Effect and Mechanism of ZLJ-6 on Focal Ischemia-reperfusion Injury in Rats

作　　者：陈颖[1] 季晖[1] 赖宜生[2] 张奕华[2] 庄佩[1] 

机构地区：[1]中国药科大学药理学教研室,江苏南京210009 [2]中国药科大学新药研究中心,江苏南京210009

出　　处：《药学进展》2009年第2期79-84,共6页Progress in Pharmaceutical Sciences

基　　金：江苏省普通高校研究生科研创新计划资助项目(CX07B-235z)

摘　　要：目的:考察化合物ZLJ-6对大鼠局灶性脑缺血再灌注损伤的保护作用,并探讨其可能的作用机制。方法:将50只健康雄性大鼠,随机分为假手术组、缺血-再灌注模型组、阿司匹林(10 mg·kg-1)阳性对照组、ZLJ-6(20 mg·kg-1)高剂量组和ZLJ-6(10 mg·kg-1)低剂量组。以线栓法制作大鼠大脑中动脉缺血再灌注模型。造模后24小时,进行神经功能评分,并断头取脑制备组织匀浆,测定丙二醛和谷氨酸的含量以及超氧化物歧化酶、髓过氧化物酶、一氧化氮合酶和诱导型一氧化氮合酶的活性。结果:与模型组比较,阳性对照组和ZLJ-6高剂量组大鼠的神经功能评分均明显改善(P<0.05),ZLJ-6高、低剂量组大鼠脑中髓过氧化物酶活性均显著降低(P<0.01),ZLJ-6高剂量组大鼠脑中一氧化氮合酶活性降低(P<0.05),ZLJ-6低剂量组大鼠脑中诱导型一氧化氮合酶活性和丙二醛含量显著降低(P<0.01和P<0.05);ZLJ-6对大鼠脑中超氧化物歧化酶活性和谷氨酸含量无明显影响。结论:化合物ZLJ-6对大鼠脑缺血再灌注损伤具有一定的保护作用,其作用机制可能与抑制缺血再灌注时中性粒细胞向脑组织浸润和抑制一氧化氮合酶活性有关。Objective： To investigate the protective effects and mechanisms of ZLJ-6 on focal cerebral ischemia-reperfusion in rats. Methods： Fifty healthy male rats were randomly divided into the sham-operation group, ischemia-reperfusion model group, aspirin （ 10 mg·kg^-1） control group, a high dose of ZLJ-6 （20 mg·kg^-1） group and a low dose of ZLJ-6 （10 mg·kg^-1） group. The middle cerebral artery occlusion （MCAO） model was made by suture method. The neurological score was measured after 24 hours, and then, the brain tissue homogenate of beheaded rats was prepared for the measurement of malondialdehyde （MDA）, glutamate （Glu） content, superoxide dismutase （SOD）, myeloperoxidase （MPO）, nitric oxide synthase （NOS） and inducible nitric oxide synthase （iNOS） activity. Results： Compared with ischemia model group, the neurological scores were improved in aspirin control group and the ZLJ-6 group with high dose （ P 〈 0.05）. The activity of MPO was dramatically reduced by the high and low doses of ZLJ-6 compared with the model group （ P 〈 0.01）. The high dose of ZLJ-6 reduced the activity of NOS （ P 〈 0.05）, and the low dose of ZLJ-6 dramatically reduced the activity of iNOS（P 〈0.01） and decrease the content of MDA（ P 〈0.05）. It has no effect on SOD and Glu. Conclusion： ZLJ-6 has neuroprotective effects for the ischemia-reperfusion injury rats. Its mechanism might be attributed to its effects of weakening the infiltration of neutrophils into brain tissue and inhibiting NOS activity.

关 键 词：咪唑酮类化合物ZLJ-6 脑缺血再灌注损伤 大脑中动脉阻塞模型 髓过氧化物酶 一氧化氮合酶 

分 类 号：R96[医药卫生—药理学]