半胱氨酰白三烯受体拮抗剂对全脑缺血再灌注慢性损伤的作用  

Effects of cysteinyl leukotrienes receptor antagonists on chronic brain injury after global cerebral ischemia/reperfusion

作　　者：王浩[1] 郭红刚[2] 楼琦[2] 石巧娟[2] WANG Hao;GUO Honggang;LOU Qi;SHI Qiaojuan(Department of Neurology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China;Laboratory Animal Center, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China)

机构地区：[1]浙江省立同德医院神经内科,浙江杭州310012 [2]浙江省医学科学院实验动物中心,浙江杭州310013

出　　处：《浙江大学学报（医学版）》2018年第1期19-26,共8页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金(31301933);浙江省自然科学基金(LQ15H090005);浙江省科技计划项目(2014C37011);浙江省医药卫生科技计划(2015117570;201477310)

摘　　要：目的:研究半胱氨酰白三烯受体(Cys LTR)拮抗剂普鲁司特和HAMI3379对全脑缺血再灌注慢性损伤的保护作用及相关作用机制。方法:40只体质量为45~65 g的清洁级健康雄性长爪沙鼠分为手术对照组、模型对照组、普鲁司特组和HAMI 3379组,每组10只。采用结扎双侧颈总动脉10 min再灌注法制作全脑缺血再灌注损伤模型。普鲁司特组和HAMI 3379组于术前30 min和术后30 min、4 h、12 h分别腹腔注射普鲁司特和HAMI 3379,第二天起每天分别给药一次,连续给药5 d。于全脑缺血再灌注24 h和14 d时对各组的神经症状和功能进行评分;尼氏染色法观察再灌注14 d时各组大脑皮层神经元的形态和数量;免疫组织化学染色检测再灌注14 d时各组大脑皮层小胶质细胞和星形胶质细胞激活情况。结果:30只长爪沙鼠中,21只造模成功,其中模型对照组7只,普鲁司特组6只,HAMI 3378组8只。与模型对照组比较,普鲁司特组和HAMI 3379组术后24 h神经症状评分降低(均P<0.01),术后14 d普鲁司特组和HAMI 3379组的神经症状评分较模型对照组亦有改善的趋势,但差异均无统计学意义(均P>0.05);普鲁司特组和HAMI 3379组在这两个时间点的神经功能评分均高于模型对照组(P<0.05或P<0.01)。普鲁司特组和HAMI 3379组大脑皮层神经元损伤较模型对照组减轻,存活神经元密度与模型对照组差异有统计学意义(均P<0.01)。普鲁司特组和HAMI 3379组大脑皮层小胶质细胞和星形胶质细胞增生情况较模型对照组改善(均P<0.01)。结论:普鲁司特和HAMI 3379对长爪沙鼠全脑缺血慢性损伤模型具有较持久的神经保护作用。Objective： To investigate the effects of cysteinyl leukotrienes receptor（Cys LTR） antagonists on global cerebral ischemia/reperfusion（ CI/R） injury in gerbils,and to explore its mechanism. Methods： Totally 40 gerbils weighting 45-65 g were randomized into sham,saline,Pranlukast and HAMI 3379 groups with 10 animals in each. The CI/R model was established in gerbils by bilateral common carotid occlusion for 10 min followed by reperfusion. After ischemia,the Cys LTR antagonists Pranlukast（0. 1 mg/kg） and HAMI 3379（0. 1 mg/kg） were injected intraperitoneally for 5 consecutive days in the last two groups,while the former two groups were injected with saline only（10 m L/kg）. After 24 h or 14 d reperfusion,neurological deficit score was evaluated and the behavioral dysfunction was assessed,respectively. And 14 d after reperfusion,the neuron morphology of cerebral cortex was observed in brain sections stained with Cresyl violet. In addition,the Iba-1（ microgila） and GFAP（ astrocyte）positive cells in cerebral cortex were observed by using immunohistochemitry method.Results： CI/R models were successfully established in 21 out of 30 gerbils with 7 in saline group,6 in Pranlukast group,and 8 in HAMI 3379 group. Compared with saline group, Pranlukast and HAMI 3379 significantly attenuated neurological deficits,improved the behavioral function 24 h after reperfusion（ all P〈0. 01）; Pranlukast and HAMI 3379 also significantly improved the behavioral function 14 days after reperfusion（P〈0. 05 or P〈0. 01）. Compared with saline group,the neurological symptom scores in Pranlukast and HAMI 3379 groups presented a trend of amelioration 14 d after reperfusion,but it was not significant（ P〉0. 05）. In addition,Pranlukast and HAMI3379 also inhibited the neuron loss and injury,suppressed microgila and astrocyte activation 14 d after reperfusion（ all P〈0. 01）. Conclusion： Cys LTR antagonists Pranlukast and HAMI 3379 have long-term neuroprotective effect on chronic brain injury in

关 键 词：白三烯拮抗剂/药理学 半胱氨酸 沙丁胺醇/治疗应用 脑缺血/病理生理学 再灌注损伤/药物作用 神经元/药物作用 疾病模型 动物 沙鼠亚科 

分 类 号：R743[医药卫生—神经病学与精神病学] R96[医药卫生—临床医学]