摘要
目的:采用大鼠脑梗死模型,考察静脉注射阿替普酶(rt-PA)溶栓后基质金属蛋白酶9(MMP-9)、组织纤溶酶原激活物与纤溶酶原激活物抑制因子的比值(t-PA/PAI-1),血管性血友病因子(VWF)、凝血八因子(FⅧ)、凝血七因子(FⅦ)与颅内出血不良反应的相关性。方法:大鼠被随机分为3组:阿替普酶组、对照组、假手术组,阿替普酶组为成功构建大脑中动脉血栓栓塞模型后静脉注射阿替普酶;对照组为成功构建大脑中动脉血栓栓塞模型;假手术组为仅进行颈动脉暴露不进行血栓栓塞操作,手术后对大鼠进行神经功能评价。阿替普酶组分别在造模前、造模后2 h、给药后4 h采血,其他两组采血时间与阿替普酶组对应。比较三组间血浆内MMP-9、t-PA/PAI-1、VWF、FⅧ、FⅦ的含量。采血后对大鼠进行灌注取脑,脑组织切片进行TTC染色,在白色脑梗死区域内有红色出血点及血肿认定为出血。阿替普酶组大鼠根据是否发生颅内出血,分为出血组与未出血组,并进一步比较两组间MMP-9、t-PA/PAI-1、VWF、FⅧ、FⅦ的变化差异及其与颅内出血的相关性。结果:阿替普酶组、对照组、假手术组各28只,其中阿替普酶组出血8只;对照组出血2只;假手术组出血0只。血浆中的MMP-9、t-PA/PAI-1、VWF、FⅧ、FⅦ在3组内3个时间点均无显著性差异(P>0.05),且组间比较均无显著性差异(P>0.05);进一步比较阿替普酶组出血动物与未出血动物血浆中的MMP-9、t-PA/PAI-1、VWF、FⅧ、FⅦ,未发现统计学差异(P>0.05)。结论:使用阿替普酶溶栓后,通过检测血浆中的MMP-9、t-PA/PAI-1、VWF、FⅦ、FⅧ,难以预测溶栓后出血不良反应的发生。
OBJECTIVE To investigate the relationship between matrix metalloproteinase 9(MMP-9),tissue plasminogen activator to plasminogen activator inhibitor(t-PA/PAI-1),von Willebrand factor(VWF),factor VIII(FVIII),factor VII(FVII)and adverse reactions of intracranial hemorrhage after intravenous alteplase(rt-PA)thrombolysis in rats.METHODS The rats were randomly divided into three groups:alteplase group,control group,and the sham operation group.In alteplase group,alteplase was intravenously injected after the middle cerebral artery thromboembolism model was successfully constructed;in control group,the middle cerebral artery thromboembolism model was successfully constructed;in sham-operated group,only carotid artery exposure was performed without thromboembolism procedure,and the neurological function of rats was evaluated after surgery.After blood sampling,the rats were perfused and the brain tissue sections were stained with TTC.The red hemorrhagic spots and hematomas in the white cerebral infarction area were considered as hemorrhage.Rats in alteplase group were divided into bleeding group and non-bleeding group according to whether intracranial hemorrhage occurred or not,and the changes of MMP-9,t-PA/PAI-1,VWF,FVIII,FVII and their correlation with intracranial hemorrhage were further compared between the two groups.RESULTS The rats in each group were 28.The number of hemorrhage rats was 8 in the administration group,2 in the modeling group,0 in the sham operation group.MMP-9,t-PA/PAI-1,VWF,FVIII,and FVII in plasma were not significantly different at any of the three time points in the three groups(P>0.05),and there were no significant differences between the groups(P>0.05);further comparison of MMP-9,t-PA/PAI-1,VWF,FVIII,and FVII in plasma between animals with and without hemorrhage in the alteplase group revealed no statistically significant differences(P>0.05).CONCLUSION It is difficult to predict hemorrhage risk after intravenous injection of Alteplase by detecting the contents changes of MMP-9,t-PA/PAI-1,VWF,F�
作者
欧会清
邱金雨
韩瑶瑶
孟佳雪
贺帅
OU Hui-qing;QIU Jin-yu;HAN Yao-yao;MENG Jia-xue;HE Shuai(Zhujiang Hospital of the South-ern Medical University,Guangdong Guangzhou 510280,China;Jinan University,Guangdong Guangzhou 510632,China)
出处
《中国医院药学杂志》
CAS
北大核心
2020年第4期397-400,405,共5页
Chinese Journal of Hospital Pharmacy
基金
广东省科技计划项目(编号:2014A020212671)。
