摘要
目的探讨半胱氨酰白三烯受体拮抗剂(普鲁司特、HAMI 3379)对长爪沙鼠全脑缺血再灌注损伤的保护作用及其作用机制。方法采用结扎双侧颈总动脉缺血10 min再灌注24 h,建立长爪沙鼠全脑缺血再灌注损伤模型,随机分为假手术组、模型组、普鲁司特、HAMI 3379组,每组20只,术前3 d开始腹腔注射给药,1次/日,术前30 min给药1次。观察再灌注24 h神经症状及功能;尼氏染色法观察皮层及海马区神经元;免疫印迹法检测皮层、海马中自噬相关蛋白beclin-1及LC3的表达情况;电镜观察海马区自噬小体。结果与模型组比较,普鲁司特、HAMI 3379组可提高神经症状评分,减少神经功能损伤,减轻皮层及海马区神经元损伤及丢失,减少自噬相关蛋白beclin-1及LC3的表达及海马区自噬小体的数量。结论半胱氨酰白三烯受体拮抗剂通过下调大脑皮层、海马区的自噬减轻长爪沙鼠全脑缺血再灌注损伤。
Objective Cysteinyl leukotrienes are potent inflammatory mediators. Their actions are mediated by specific receptors,the Cys LT receptors（ CysLT_1R and CysLT_2R）,which have been cloned and characterized. In this study,we investigated the protective effects of the Cys LTR antagonist Pranlukast and HAMI 3379 on global cerebral ischemia/reperfusion（ CI/R） injury in gerbils and its underlying mechanisms. Methods The gerbil model of CI/R was established by bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion. Then the animals were equally randomized into four groups： sham,model,Pranlukast（ 0. 1 mg/kg） and HAMI 3379（ 0. 1 mg/kg） groups. The later two groups were treated with intraperitoneal injection of Pranlukast and HAMI 3379,respectively,once daily for 4 days before carotid artery occlusion,while the former two groups with saline only,all at 10 m L/kg. After 24 h reperfusion,neurological deficit scores were observed and the behavioral dysfunction was assessed. The neuron morphology of cerebral cortex and CA1 subregion of hippocampus were observed in brain sections stained with cresyl violet. The expression of autophagy-related proteins beclin-1 and LC3 in the homogenate of cerebral cortex and hippocampus were determined using western blotting analysis. The ultrastructure of autophagosomes in the CA1 subregion of hippocampus was observed by electron microscopy.Results Compared with the model group,Pranlukast and HAMI 3379 attenuated neurological deficits,improved the behavioral dysfunction,inhibited the neuron injury and loss,decreased the expression of autophagy-related protein beclin-1 and LC3 and the number of autophagosomes. Conclusions cysteinyl Leukotriene receptor antagonist Pranlukast and HAMI3379 can alleviate global cerebral ischemia/reperfusion injury in gerbils. The protective effects of Pranlukast and HAMI3379 appear to be associated with the inhibition of autophagy.
作者
石巧娟
郭红刚
楼琦
卢领群
潘若真
应华忠
周文伟
褚晓峰
SHI Qiaojuan;GUO Honggang;LOU Qi;LU Lingqun;PAN Ruozhen;YING Huazhong;ZHOU Wenwei;CHU Xiaofeng(Zhejiang Academy of Medical Sciences Center of Laboratory Animals, Key Laboratory of Experimental Animal and Safety Research of Zhejiang Province, Zhejiang Hangzhou 310013,China;Zhejiang Academy Medical Sciences, Zhejiang Public Service Platform for Laboratory Animals, Zhejiang Hangzhou 310013)
出处
《中国实验动物学报》
CAS
CSCD
北大核心
2018年第1期57-64,共8页
Acta Laboratorium Animalis Scientia Sinica
基金
国家科技支撑计划项目(No.2015BAI09B01-02)
国家自然科学基金项目(No.31301933,No.81401566)
浙江省医药卫生计划项目(No.201477310)
省科技计划项目(No.2014C37011)
关键词
长爪沙鼠
全脑缺血
普鲁司特
HAMI
3379
自噬
gerbil
global cerebral ischemia
reperfusion injury
pranlukast
HAMI 3379
autophagy
