银杏内酯注射液及其组分对大鼠缺血性脑卒中模型作用比较及对突触后致密物95表达的影响  

Effect of Ginkgolides Injection and its active constituents on postsynaptic density 95 in acute cerebral ischemic stroke

作　　者：邬春久 兰新新 刘科 丁建花[2] 李慧琴 胡刚[2] HU Chunjiu;LAN Xinxin;LIU Ke;DING Jianhua;LI Huiqin;HU Gang(Chengdu baiyu pharmaceutical Co., Ltd., Chengdu 641000, China;Nanjing Medical University, Nanjing 211166, China;Tianjin Pharmaceutical Research Institute, Tianjin 300193, 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 [3]天津药物研究院,天津300193

出　　处：《药物评价研究》2019年第6期1110-1114,1145,共6页Drug Evaluation Research

摘　　要：目的研究银杏内酯注射液(GIs)及其主要组分银杏内酯B(GB)和白果内酯(BB)对急性缺血性脑损伤的改善作用,以及GIs对突触后致密物95(PSD95)蛋白表达的影响。方法①采用Longa法制备大鼠大脑中动脉阻塞(tMCAO)模型,于缺血再灌注1 h后给予GIs(2.5、5.0 mg/kg)、GB(1.25、2.50 mg/kg)、BB(1.25、2.50 mg/kg),每天给药2次,连续给药3 d。于术后24、48、72 h各进行神经功能评分1次;TTC染色法测定脑梗死体积;称大鼠干湿质量,测定脑组织含水量。②大鼠随机分为假手术组、GIs单给药(2.5 mg/kg)组、模型组和GIs治疗(tMCAO+GIs 2.5 mg/kg)组,制备tMCAO模型,再灌1 h后开始ip给药,3 d内每天给药2次。分别于再灌注后24、72 h取脑,Western blotting法检测缺血半影区PSD 95蛋白表达水平。结果①与模型组比较,GIs及其主要组分GB、BB均显著改善tMCAO模型大鼠神经运动功能障碍,减少脑梗死体积,降低脑水肿(P<0.05、0.01);同等剂量下(2.5 mg/kg),GIs治疗效应优于单组份GB、BB。②GIs组给药后胞浆PSD95蛋白水平均较模型组显著升高(P<0.05、0.01)。结论 GIs及其有效组分GB、BB均具有改善tMCAO大鼠急性缺血性损伤的作用,GIs的作用优于GB、BB单独用药,作用机制可能与上调PSD95蛋白表达相关。Objective To study the effects of Ginkgolides Injection(GIs) and its main components Ginkgolides B(GB) and Baiguolide(BB) on acute ischemic brain injury, and the effects of GIs on the expression of postsynaptic dense substance 95(PSD95).Methods ① A 90 min transcient middle cerebral artery occlusion model(tMCAO) was established using Longa method. Rats were randomly divided into seven groups: tMCAO group, GIs(2.5, 5.0 mg/kg) groups, GB(1.25, 2.5 mg/kg) groups and BB(1.25, 2.5 mg/kg) groups. Rats were ip administered after 1 h of reperfusion, and continuously for three days. Neurological deficit score,infarct size(TTC staining) and brain water content were measured at 72 h after reperfusion.② Rats were randomly divided into four groups: sham group, sham + GIs groups(2.5 mg/kg), tMCAO groups, and tMCAO + GIs groups(2.5 mg/kg). Rats were ip administered after 1 h of reperfusion, and continuously for three days, twice a day. The PSD 95 protein level in cerebral ischemic penumbra was measured by Western blotting at 24 and 72 h after reperfusion. Results ① Compared with model group, GIs and its main components GB and BB significantly improved neuromotor dysfunction, reduced cerebral infarction volume and brain edema in tMCAO model rats(P < 0.05, 0.01);At the same dose(2.5 mg/kg), the effect of GIs treatment was better than that of single component GB and BB.② The level of PSD95 protein in GIs group was significantly higher than that in model group(P < 0.05,0.01). Conclusion GIs and its active constituents, GB and BB have therapeutical effect in acute ischemic brain injury induced by tMCAO in rats, and GIs was better than single treatment of GB and BB. The mechanism may be related to the up-regulation of PSD95 protein expression.

关 键 词：银杏内酯注射液 银杏内酯B 白果内酯 脑缺血再灌注 神经保护 PSD95 

分 类 号：R962.2[医药卫生—药理学]