蝙蝠葛酚性碱调节p-NR1和NR2A对脑缺血再灌注大鼠发挥神经保护作用  

Neuroprotective effects of phenolic alkaloids of Menispermum dauricum on rats with ischemia reperfusion by regulating expression of p-NR1 and NR2A

作　　者：章歌雅[1] 李燕利[1] 王妍[2] 陈占高 严玲玲[4] 何治[1] 

机构地区：[1]三峡大学医学院三峡大学中药药理三级实验室,湖北宜昌443002 [2]佛山市第一人民医院药剂科,广东佛山528000 [3]武汉名实生物医药科技有限责任公司,湖北武汉430070 [4]武汉科技大学附属天佑医院,湖北武汉430070

出　　处：《中国医院药学杂志》2017年第7期579-582,共4页Chinese Journal of Hospital Pharmacy

基　　金：湖北省高等学校优秀中青年科技创新团队计划项目(编号:T201403)

摘　　要：目的:探讨蝙蝠葛酚性碱(phenolic alkaloids of Menispermum dauricum,PAMD)对脑缺血再灌注大鼠的神经保护作用及其机制。方法:大鼠局灶性脑缺血模型采用大脑中动脉线栓法制作。动物随机分为假手术组,缺血再灌注组,PAMD低(25 mg·kg^(-1))、中(50 mg·kg^(-1))、高(75 mg·kg^(-1))剂量治疗组。持续栓塞2 h拔出线栓,再灌注4 h,然后断头取脑。干湿重法求出脑组织含水量,伊文思蓝含量测定法观察血脑屏障通透性。分离皮层组织,免疫印迹方法检测NR1和NR2A及各自对应的磷酸化蛋白。结果:(1)PAMD可以减少脑缺血再灌注大鼠脑组织含水量(P<0.05),降低脑缺血再灌注大鼠血脑屏障通透性(P<0.05);(2)与假手术组比较,缺血再灌注组NR1,NR2A,p-NR2A表达无明显变化,p-NR1表达减少(P<0.05);与缺血再灌注组比较,PAMD使p-NR1表达增多(P<0.05),NR2A表达减少(P<0.05)。结论:PAMD可通过调节p-NR1和NR2A对脑缺血再灌注大鼠发挥神经保护作用。OBJECTIVE To investigate the neuroprotective effects and the underlying mechanisms of phenolic alkaloids of Menispermum dauricum （PAMD） on cerebral ischemia-reperfusion in vivo in rats.METHODS The cerebral ischemia rat model was made by right middle cerebral artery occlusion for 2 h and reperfusion for 4 h. The Sprague Dawley rats were randomly divided into the sham-operative group, the cerebral ischemia model group, PAMD （25 mg·kg-1） group, PAMD （50 mg·kg-1） and PAMD （75 mg·kg-1） group. PAMD was intragastrically given every day for a week before the ischemia. The extent of edema was determined by weighing method. The permeability of the blood brain barrier was evaluated by measuring Evans Blue （EB） contents in the brain with spectrophotometer. Expressions of NMDAR1 （NR1）, NMDAR2A （NR2A）, phosphor-NMDAR1 （p-NR1） and phosphor-NMDAR2A （p-NR2A） were assayed by Western blotting.RESULTS PAMD ameliorated the edema and reduced the permeability of blood-brain barrier （P〈0.05）. Compared with the sham-operative group, the expression of p-NR1 in cortex was decreased significantly in the ischemia group （P〈0.05）, while NR1, NR2A and p-NR2A proteins were not obviously changed. Compared with the cerebral ischemia model group, the expression of p-NR1 in cortex was up-regulated by PAMD, while NR2A was down-regulated by PAMD.CONCLUSION PAMD alleviates brain injury caused by ischemia-reperfusion in rats, which is partly mediated by p-NR1 and NR2A.

关 键 词：蝙蝠葛酚性碱 脑缺血再灌注 神经保护 

分 类 号：R34[医药卫生—基础医学]