OBJECTIVE To investigate the thrombolytic and antiplatelet effects of a novel plasminogen activator from the venom of Gloydius brevicaudus viper(GBV-PA)in vitro and in vivo.METHODS Thrombolytic experiments were perfor...OBJECTIVE To investigate the thrombolytic and antiplatelet effects of a novel plasminogen activator from the venom of Gloydius brevicaudus viper(GBV-PA)in vitro and in vivo.METHODS Thrombolytic experiments were performed in rabbit models of ear vein thrombosis and carotid artery thrombosis,and in dog model of acute cerebral infarction.Inhibition of thrombus formation was evaluated in rat inferior vena cava thrombosis model and ferric chloride-induced arterial thrombosis.In vitro,we assayed the antithrombotic effect of GBV-PA on rabbit blood clots,euglobulin lysis time(ELT)of rabbit plasma,and on ADP-induced platelet aggregation.RESULTS GBV-PA intravenous administ ration significantly reduced vascular recanalization times of rabbit ear veins thrombosis and thrombus weight of rabbit carotid artery thrombosis.The arterial recanalization rates were dose-and time-dependently improved after administration of GBV-PA in canine acute cerebral infarction model.Thrombus length and weight was significantly reduced by GBV-PA both in rat inferior vena cava and ferric chloride-induced arterial thrombosis models.Thrombus formation of blood of rabbits they were administrated with GBV-PA was also inhibited.GBV-PA radically reduced plasma ELT of rabbit′s blood clots.ADP-induced platelet aggregation was inhibited by GBV-PA in a dose-dependent manner with a half-maximal inhibitory concentration of 19.9μg·mL-1.CONCLUSION This study demonstrates that GBV-PA is a thrombolytic and antiplatelet agent.It has significant antithrombotic effects on various in vitro and in vivo experimental models of thrombosis.The mechanisms that underline its antithrombotic effects were related to GBV-PA′s capabilities of increasing fibrinolytic activities and inhibition of platelet aggregation.展开更多
目的探讨颅内大动脉闭塞患者急性期细胞因子水平及其与脑梗死体积和功能预后的相关性。方法纳入2021年1月至2023年12月河南大学淮河医院神经外科颅内大动脉闭塞患者168例,记录患者发病后90 d内功能预后情况,并根据患者预后情况分为预后...目的探讨颅内大动脉闭塞患者急性期细胞因子水平及其与脑梗死体积和功能预后的相关性。方法纳入2021年1月至2023年12月河南大学淮河医院神经外科颅内大动脉闭塞患者168例,记录患者发病后90 d内功能预后情况,并根据患者预后情况分为预后良好组54例和预后不良组114例,收集2组患者急性期细胞因子水平及脑梗死体积,分析颅内大动脉闭塞患者急性期细胞因子水平及其与脑梗死体积和功能预后的相关性。结果预后不良组高血压比例、发病至入院时间、入院时美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、脑梗死核心体积、白细胞介素(interleukin,IL)-1、IL-6、IL-8、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、金属基质蛋白酶9(matrix metalloprotein 9,MMP-9)、活性氧、血管内皮生长因子(vascular endothelial growth factor,VEGF)水平明显高于预后良好组,差异有统计学意义(P<0.05,P<0.01)。Pearson相关性分析显示,颅内大动脉闭塞患者脑梗死核心体积与IL-1、IL-6、IL-8、TNF-α、MMP-9、活性氧、VEGF水平呈正相关(P<0.01)。多因素logistic回归分析显示,在去除混杂(发病至入院时间、入院时NIHSS评分、脑梗死核心体积)后,细胞因子IL-1(OR=1.723,95%CI:1.333~2.227,P=0.000)、IL-6(OR=1.475,95%CI:1.190~1.830,P=0.000)、TNF-α(OR=1.392,95%CI:1.167~1.661,P=0.000)、MMP-9(OR=1.062,95%CI:1.031~1.094,P=0.000)、活性氧(OR=1.020,95%CI:1.007~1.034,P=0.003)仍是颅内大动脉闭塞患者功能预后不良的独立影响因素。结论脑梗死核心体积与IL-1、IL-6、IL-8、TNF-α、MMP-9、活性氧、VEGF均存在正相关性,急性期内细胞因子IL-1、IL-6、TNF-α、MMP-9、活性氧是颅内大动脉闭塞患者功能预后不良的独立影响因素。展开更多
目的探讨血栓抽吸联合冠状动脉内注射重组人TNK组织型纤溶酶原激活剂对老年ST段抬高型心肌梗死患者急诊经皮冠状动脉介入治疗术中冠状动脉微循环及心功能的影响。方法回顾性选取2021年1月至2023年10月于天津市第三中心医院就诊的并行急...目的探讨血栓抽吸联合冠状动脉内注射重组人TNK组织型纤溶酶原激活剂对老年ST段抬高型心肌梗死患者急诊经皮冠状动脉介入治疗术中冠状动脉微循环及心功能的影响。方法回顾性选取2021年1月至2023年10月于天津市第三中心医院就诊的并行急诊经皮冠状动脉介入治疗的老年ST段抬高型心肌梗死患者90例,根据经皮冠状动脉介入治疗术中介入策略不同分为单纯血栓抽吸组(抽吸组)46例和血栓抽吸联合冠状动脉内注射重组人TNK组织型纤溶酶原激活剂组(联合组)44例。比较2组一般临床资料,术后90 min ST段回落指数≥70%比例,术后即刻心肌梗死溶栓试验(thrombolysis in myocardial infarction,TIMI)血流分级,术后TIMI心肌灌注分级,校正的TIMI血流帧数,心脏超声指标以及住院期间主要不良心血管事件及出血事件。结果联合组术后ST段回落≥70%、术后即刻TIMI血流分级3级、术后TIMI心肌灌注分级3级比例显著高于抽吸组,校正的TIMI血流帧数显著低于抽吸组(P<0.05);抽吸组术后1周的左心室射血分数显著低于联合组[(52.5±6.2)%vs(58.3±6.4)%,P<0.05],联合组术后1周左心室舒张末期内径显著低于抽吸组[(44.1±3.9)mm vs(51.9±2.5)mm,P<0.05];联合组住院期间主要不良心血管事件发生率显著低于抽吸组(20.5%vs 37.0%,P<0.05)。结论在应用抽吸导管的基础上配合冠状动脉内注射重组人TNK组织型纤溶酶原激活剂可有效降低老年ST段抬高型心肌梗死患者冠状动脉内血栓负荷,改善心肌微循环灌注,降低住院期间主要不良心血管事件发生率且不增加出血风险。展开更多
基金The project supported by the Natural Science Foundation of Fujian Province(2007J0008and C0720002)the Training Program of Fujian Excellent Talents in University
文摘OBJECTIVE To investigate the thrombolytic and antiplatelet effects of a novel plasminogen activator from the venom of Gloydius brevicaudus viper(GBV-PA)in vitro and in vivo.METHODS Thrombolytic experiments were performed in rabbit models of ear vein thrombosis and carotid artery thrombosis,and in dog model of acute cerebral infarction.Inhibition of thrombus formation was evaluated in rat inferior vena cava thrombosis model and ferric chloride-induced arterial thrombosis.In vitro,we assayed the antithrombotic effect of GBV-PA on rabbit blood clots,euglobulin lysis time(ELT)of rabbit plasma,and on ADP-induced platelet aggregation.RESULTS GBV-PA intravenous administ ration significantly reduced vascular recanalization times of rabbit ear veins thrombosis and thrombus weight of rabbit carotid artery thrombosis.The arterial recanalization rates were dose-and time-dependently improved after administration of GBV-PA in canine acute cerebral infarction model.Thrombus length and weight was significantly reduced by GBV-PA both in rat inferior vena cava and ferric chloride-induced arterial thrombosis models.Thrombus formation of blood of rabbits they were administrated with GBV-PA was also inhibited.GBV-PA radically reduced plasma ELT of rabbit′s blood clots.ADP-induced platelet aggregation was inhibited by GBV-PA in a dose-dependent manner with a half-maximal inhibitory concentration of 19.9μg·mL-1.CONCLUSION This study demonstrates that GBV-PA is a thrombolytic and antiplatelet agent.It has significant antithrombotic effects on various in vitro and in vivo experimental models of thrombosis.The mechanisms that underline its antithrombotic effects were related to GBV-PA′s capabilities of increasing fibrinolytic activities and inhibition of platelet aggregation.
文摘目的探讨颅内大动脉闭塞患者急性期细胞因子水平及其与脑梗死体积和功能预后的相关性。方法纳入2021年1月至2023年12月河南大学淮河医院神经外科颅内大动脉闭塞患者168例,记录患者发病后90 d内功能预后情况,并根据患者预后情况分为预后良好组54例和预后不良组114例,收集2组患者急性期细胞因子水平及脑梗死体积,分析颅内大动脉闭塞患者急性期细胞因子水平及其与脑梗死体积和功能预后的相关性。结果预后不良组高血压比例、发病至入院时间、入院时美国国立卫生研究院卒中量表(National Institute of Health Stroke Scale,NIHSS)评分、脑梗死核心体积、白细胞介素(interleukin,IL)-1、IL-6、IL-8、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、金属基质蛋白酶9(matrix metalloprotein 9,MMP-9)、活性氧、血管内皮生长因子(vascular endothelial growth factor,VEGF)水平明显高于预后良好组,差异有统计学意义(P<0.05,P<0.01)。Pearson相关性分析显示,颅内大动脉闭塞患者脑梗死核心体积与IL-1、IL-6、IL-8、TNF-α、MMP-9、活性氧、VEGF水平呈正相关(P<0.01)。多因素logistic回归分析显示,在去除混杂(发病至入院时间、入院时NIHSS评分、脑梗死核心体积)后,细胞因子IL-1(OR=1.723,95%CI:1.333~2.227,P=0.000)、IL-6(OR=1.475,95%CI:1.190~1.830,P=0.000)、TNF-α(OR=1.392,95%CI:1.167~1.661,P=0.000)、MMP-9(OR=1.062,95%CI:1.031~1.094,P=0.000)、活性氧(OR=1.020,95%CI:1.007~1.034,P=0.003)仍是颅内大动脉闭塞患者功能预后不良的独立影响因素。结论脑梗死核心体积与IL-1、IL-6、IL-8、TNF-α、MMP-9、活性氧、VEGF均存在正相关性,急性期内细胞因子IL-1、IL-6、TNF-α、MMP-9、活性氧是颅内大动脉闭塞患者功能预后不良的独立影响因素。
文摘目的探讨血栓抽吸联合冠状动脉内注射重组人TNK组织型纤溶酶原激活剂对老年ST段抬高型心肌梗死患者急诊经皮冠状动脉介入治疗术中冠状动脉微循环及心功能的影响。方法回顾性选取2021年1月至2023年10月于天津市第三中心医院就诊的并行急诊经皮冠状动脉介入治疗的老年ST段抬高型心肌梗死患者90例,根据经皮冠状动脉介入治疗术中介入策略不同分为单纯血栓抽吸组(抽吸组)46例和血栓抽吸联合冠状动脉内注射重组人TNK组织型纤溶酶原激活剂组(联合组)44例。比较2组一般临床资料,术后90 min ST段回落指数≥70%比例,术后即刻心肌梗死溶栓试验(thrombolysis in myocardial infarction,TIMI)血流分级,术后TIMI心肌灌注分级,校正的TIMI血流帧数,心脏超声指标以及住院期间主要不良心血管事件及出血事件。结果联合组术后ST段回落≥70%、术后即刻TIMI血流分级3级、术后TIMI心肌灌注分级3级比例显著高于抽吸组,校正的TIMI血流帧数显著低于抽吸组(P<0.05);抽吸组术后1周的左心室射血分数显著低于联合组[(52.5±6.2)%vs(58.3±6.4)%,P<0.05],联合组术后1周左心室舒张末期内径显著低于抽吸组[(44.1±3.9)mm vs(51.9±2.5)mm,P<0.05];联合组住院期间主要不良心血管事件发生率显著低于抽吸组(20.5%vs 37.0%,P<0.05)。结论在应用抽吸导管的基础上配合冠状动脉内注射重组人TNK组织型纤溶酶原激活剂可有效降低老年ST段抬高型心肌梗死患者冠状动脉内血栓负荷,改善心肌微循环灌注,降低住院期间主要不良心血管事件发生率且不增加出血风险。
