银杏内酯注射液抑制脑缺血再灌注模型大鼠内质网应激和自噬  

Ginkgolides injection inhibits endoplasmic reticulum stress and attenuates autophagy in rat brain induced by cerebral ischemia reperfusion

作　　者：兰新新 曹磊[1] 王林晓[1] 丁建花[1] 范益[1] 胡刚[1] 

机构地区：[1]南京医科大学药理学系

出　　处：《中国临床药理学与治疗学》2015年第6期634-639,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金："重大新药创制"国家科技重大专项--防治神经退行性疾病;自身免疫性疾病和恶性肿瘤新药的临床前药效学评价技术平台(2012ZX09304001);天然药物活性组分与药效国家重点实验室开放课题项目(SKLNMKF201403)

摘　　要：目的:探讨银杏内酯注射液(ginkgolides injection,GIs)对大鼠脑缺血再灌注损伤的保护作用及其可能机制。方法:采用Longa法制备大鼠短暂性大脑中动脉阻塞(t MCAO)/再灌注损伤模型,于缺血再灌注1 h后腹腔注射(i.p.,bid)不同剂量的GIs(1.25、2.5、5 mg/kg),连续治疗3 d并进行神经功能评分,干湿重法测定脑组织含水量,TTC染色法测定脑梗死体积;制备大鼠t MCAO模型,于再灌注1 h给予GIs(2.5 mg/kg),24 h和72 h时取样,Western Blotting法检测缺血半影区内质网应激、自噬等相关蛋白表达。结果:GIs(2.5、5 mg/kg)显著改善t MCAO模型大鼠神经运动功能障碍,减轻脑水肿,减小脑梗死体积;GIs显著抑制缺血再灌注损伤引起的大鼠缺血半影区内质网应激和自噬水平上升。结论:GIs减轻脑缺血再灌注急性期损伤,其机制与抑制内质网应激和自噬相关。AIM： To investigate the neuroprotective effects of ginkgolides injection（ GIs） against ischemic stroke-induced injury and further explore the possible mechanisms concerned. METHODS：The modified method of Zea Longa was used to establish the transient middle cerebral artery occlusion（ t MCAO） model in rats. GIs was injected intraperitoneally（ i. p.,bid,3 d） to rats 1h after onset of reperfusion with different doses（ 1. 25,2. 5 and 5mg / kg）. The neurological deficits were assessed in each group after cerebral ischemia. Brain water content was measured by wet / dry weight method and infarct volume was observed by TTC staining. Western Blot was used to evaluate the expression level of protein related to ER stress and autophagy in penumbra region of rats treated with GIs（ 2. 5 mg / kg） at 24 h and 72 h after reperfusion. RESULTS： GIs（ 2. 5and 5 mg / kg） treatment significantly reduced neurological deficits,water content,and cerebral infarct volume after stroke. GIs（ 2. 5 mg / kg） treatment protected against ischemia / reperfusion-induced ER stress and autophagy. CONCLUSION： GIs are neuroprotective against ischemic brain injury through the down regulation of ER stress and autophagy.

关 键 词：银杏内酯注射液 脑缺血再灌注损伤 神经保护 内质网应激 自噬 

分 类 号：R965.2[医药卫生—药理学]