摘要
目的:探讨天麻醇提物(ethanol extract of Gastrodia elata,EEGE)与组织型纤溶酶原激活物(tissue plasminogen activator,rt-PA)进行联合应用后,能否在急性期保护缺血半暗带区神经细胞,延长溶栓时间窗。方法:建立大鼠栓塞性大脑中动脉闭塞(eMCAO)模型,将神经学评分在3~5分的大鼠按随机数字表法分为6组:假手术(Sham)组、模型(Model)组、4.5 h rtPA组、4.5 h rt-PA+EEGE组、6.0 h rt-PA组、6.0 h rt-PA+EEGE组、9.0 h rt-PA组、9.0 h rt-PA+EEGE组。rt-PA+EEGE组于溶栓前10 min、溶栓后6 h和12 h灌胃给予EEGE,其余各组灌胃给予等体积溶媒。除Sham组外,各组大鼠在缺血4.5、6.0和9.0 h进行rt-PA溶栓。术后24 h,进行TTC、HE、Nissl染色,并用免疫荧光检测MAP-2表达、TUNEL染色检测神经元凋亡情况。结果:给予EEGE后,与模型组比,4.5 h rt-PA组、4.5 h rt-PA+EEGE组、6.0 h rt-PA+EEGE组脑梗死率减小(P<0.01),细胞受损情况明显减轻、核固缩现象减少,神经元细胞数量增加,尼氏体数量增多,免疫荧光强度增强,缺血中心区面积变小,急性期保护缺血半暗带区面积增大。6.0 h rt-PA组与6.0 h rt-PA+EEGE组比,脑梗死率减小(P<0.05),神经元损伤减轻,尼氏体数量增加,神经元结构保持相对完整,缺血中心区面积变小,急性期保护缺血半暗带区面积有所增大。结论:EEGE与rt-PA联合应用具有延长溶栓治疗时间窗的潜在作用。
OBJECTIVE ETo investigate whether the combined application of ethanol extract of Gastrodia elata(EEGE)and recombinant tissue plasminogen activator(rt-PA)can protect neurons in the ischemic penumbra region during the acute phase and extend the thrombolytic time window.METHODS After ischemia modeling in rats by the embolic middle cerebral artery occlu-sion,rats with the neurologic function grading of 3-5 points were randomly divided into six groups:Sham group,Model group,4.5 h rt-PA group,4.5 h rt-PA+EEGE group,6.0 h rt-PA group,6.0 h rt-PA+EEGE group,9.0 h rt-PA group,9.0 h rt-PA+EEGE group.After the model was established,rats in the rt-PA thrombolysis+EEGE group were given EEGE by gavage at 10 min before thrombolysis,and 6 h and 12 h after thrombolysis.Rats in other groups were given an equal volume of sol-vent by gavage.Except for the Sham group and Model group,rats in the remaining groups were treated with rt-PA thrombolysis at 4.5,6.0 and 9.0 h after ischemia.At 24 h after operation,triphenyltetrazolium chloride(TTC)staining,hematoxylin-eosin(HE)staining,and Nissl staining were performed.Immunofluorescence was conducted to visualize microtubule-associated pro-tein 2(MAP-2)expression,and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining was used to detect neuronal apoptosis.RESULTS After giving EEGE,compared with the model group,rats in the 4.5 h rt-PA group,the 4.5 h rt-PA+EEGE group,and the 6.0 h rt-PA+EEGE group presented significantly decreased cerebral infarction area(P<O.O1),relieved cell damage and nuclear condensation,increased number of neurons,number of Nissl bodies,and immunofluores-cence intensity of MAP-2,reduced area of the ischemic center,and expanded area of the ischemic penumbra.Compared with 6.O h rt-PA+EEGE group,rats in the 6.0 h rt-PA group had significantly reduced cerebral infarction rate(P<0.05),reduced neuro-nal damage,increased number of Nissl bodies,relatively intact neuronal structure,decreased area of ischemic center,and increased area of ischemic penumbra.CONCLUSION NThe combination of EEGE and rt-PA has the potential to prolong the time window of thrombolytic therapy.
作者
陈明
杨茜
孙云兰
李云英
谭晓玉
张笑萌
胡冬雄
何芳雁
CHEN Ming;YANG Qian;SUN Yunlan;LI Yunying;TAN Xiaoyu;ZHANG Xiaomeng;HU Dongxiong;HE Fangyan(College of Traditional Chinese Medicine,Yunnan University of Chinese Medicine,Yunnan Kunming 650500,China;School of Basic Medical Sciences,Yunnan University of Chinese Medicine,Yunnan Kunming 650500,China)
出处
《中国医院药学杂志》
北大核心
2025年第21期2443-2450,共8页
Chinese Journal of Hospital Pharmacy
基金
国家自然科学基金资助项目(编号:82360784)
云南省科技厅科技计划-中医联合专项面上项目(编号:202301AZ070001-045)
云南省科技人才和平台计划(编号:202105AG070012XS23032)。
关键词
天麻醇提物
组织型纤溶酶原激活物
溶栓时间窗
缺血半暗带
ethanol extract of Gastrodia elata
tissue plasminogen activator
thrombolysis time window
ischemic pen
