银杏内酯注射液对脑缺血再灌注损伤治疗时间窗及凋亡信号通路的影响  

Effects of Ginkgolide Injection on therapeutic time window of cerebral ischemiareperfusion injury and apoptosis signaling pathway in rats

作　　者：刘科 鄢云彪 丁建花[2] 兰新新 胡刚[2] LIU Ke;YAN Yunbiao;DING Jianhua;LAN Xinxin;HU Gan(Chengdu Baiyu Pharmaceutical Co.Ltd.,Chengdu 641000,China;Nanjing Medical University,Nanjing 211166,China)

机构地区：[1]成都百裕制药股份有限公司,四川成都641000 [2]南京医科大学,江苏南京211166

出　　处：《药物评价研究》2018年第7期1169-1173,共5页Drug Evaluation Research

摘　　要：目的研究银杏内酯注射液(Ginkgolide Injection,GI)作用于大鼠脑缺血再灌注损伤的治疗时间窗及对凋亡信号通路的影响。方法采用Longa法制备大鼠大脑中动脉短暂阻塞再灌注(t MCAO)模型,(1)分别于再灌后1、3、6、9 h ip首次给予GI(2.5 mg/kg),每天给药2次,连续给药3 d,通过神经功能评分、脑梗死体积及脑组织含水量评价动物缺血损伤程度。(2)于再灌注后1 h ip给予GI(2.5 mg/kg),每天给药2次,连续给药3 d,分别于再灌注后24、72 h取脑检测缺血半影区p53、Bax、Bcl-2、Caspase 3蛋白表达水平。结果与模型组比较,(1)再灌注后1、3 h给予GI能显著降低神经功能评分、减少脑梗死体积与脑组织含水量(P<0.05、0.01),6、9 h给药大鼠脑损伤未见明显改善。(2)于再灌注后1 h给予GI显著抑制p53、Bax、Caspase 3蛋白表达,上调Bcl-2蛋白表达(P<0.05)。结论 GI对t MCAO模型大鼠的有效治疗时间在缺血再灌注后3 h内;其可能的作用机制涉及抑制凋亡信号通路的激活。Objective To investigate the effects of Ginkgolide Injection（GI） on the therapeutic time window of cerebral ischemia-reperfusion and its apoptosis signaling pathway in rats. Methods A transcient middle cerebral artery occlusion（t MCAO） model was established using Longa＇s method. In the first section of the study, GI（2.5 mg/kg） was ip administrated respectively at 1, 3, 6, and 9 h post reperfusion, two times a day for three days continuously. The degree of cerebral ischemia injury in model rats was assessed according to the extent of neurologic status, infarction volume, and water content in brain. The second section of the study was started with the dose of GI（2.5 mg/kg） to the t MCAO rats at 1 h post reperfusion, two times a day for three days continuously. Then p53, Bax, Bcl-2, and Caspase 3 in penumbra were measured with Western blotting at 24 h and 72 h post reperfusion, respectively. Results Compared with model group, the neurological deficit, infarction volume as well as edema were significantly improved in the 1 and 3 h GI treated group（P〈0.05 and 0.01）, and the brain damage of rats in the 6 and 9 h GI treated group were not significantly improved. The p53, Bax, and Caspase 3 were significantly down-regulated and the expression of Bcl-2 was significantly increased by GI administration both at 24 h and 72 h after reperfusion（P〈0.05）. Conclusion The therapeutic window of GI for transient focal cerebral ischemic injury lasts for at least 3 h, and inhibition of the apoptosis activation was involed in GI protective mechanisms.

关 键 词：银杏内酯注射液 脑卒中 治疗时间窗 凋亡信号通路 

分 类 号：R962.2[医药卫生—药理学]