目的探讨替罗非班治疗作为补充手段用于未接受静脉溶栓的急性缺血性脑卒中(AIS)患者机械取栓(MT)后静脉维持治疗的可行性与安全性。方法入选不符合静脉溶栓条件且CT血管成像证实为大动脉闭塞的87例AIS患者,其中MT+替罗非班维持(MT+T)组4...目的探讨替罗非班治疗作为补充手段用于未接受静脉溶栓的急性缺血性脑卒中(AIS)患者机械取栓(MT)后静脉维持治疗的可行性与安全性。方法入选不符合静脉溶栓条件且CT血管成像证实为大动脉闭塞的87例AIS患者,其中MT+替罗非班维持(MT+T)组44例,MT组43例。MT+T组患者采用支架取栓并在术后立即静脉泵入0.1μg·kg-1·min-1替罗非班维持24 h,之后口服抗血小板聚集药物;MT组患者采用支架取栓治疗,术后口服抗血小板聚集药物。比较两组患者术前基线资料、血管再通情况、神经功能恢复情况、术后并发症及死亡情况。结果MT+T组与MT组患者术后14 d美国国立卫生研究院卒中量表(NIHSS)评分[(7.7±2.2)分vs.(8.8±3.3)分]、术后并发症[4.55%(2/44)vs.6.98%(3/43)]及病死率[2.27%(1/44)vs.2.33%(1/43)]比较,差异均无统计学意义(P均>0.05);而MT+T组患者术后90 d改良Rankin量表(mRS)评分低于MT组[(1.7±1.0)分vs.(2.2±1.1)分,t=2.479,P=0.015]。亚组分析显示,MT+T组取栓次数>3次的患者术后14 d NIHSS评分[(8.6±3.1)分vs.(12.5±3.5)分]及术后90 d mRS评分[(1.7±1.5)分vs.(2.8±1.0)分]均低于MT组(t=2.996、2.172,P=0.006、0.040);MT+T组及MT组取栓次数≤3次的患者术后14 d NIHSS评分[(7.4±1.6)分vs.(7.2±1.5)分]及术后90 d mRS评分[(1.7±0.7)分vs.(2.0±1.1)分]比较差异均无统计学意义(t=0.441、1.362,P=0.661、0.178)。结论替罗非班可作为未接受静脉溶栓的AIS患者行3次以上支架取栓治疗后的补充手段,可有效改善患者的神经功能及预后,且不增加脑出血转化风险。展开更多
OBJECTIVE Tissue plasminogen activator(tPA) is the only approved pharmaco.logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans.formation that follows tPA treatment.Here...OBJECTIVE Tissue plasminogen activator(tPA) is the only approved pharmaco.logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans.formation that follows tPA treatment.Here,we determined whether nicotinamide mononucleotide(NMN),a key intermediate of nicotinamide adenine dinucleotide biosynthesis,affects tPA-induced haemorrhagic transformation.METHODS Middle cerebral artery occlusion(MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.When the filament was removed for reperfusion,tPA was infused via the tail vein.A single dose of NMN was injected i.p.(300 mg·kg^(-1)).Mice were killed at 24 h post ischaemia,and their brains were evaluated for brain infarction,oedema,haemoglobin content,apoptosis,neuroinflammation,blood-brain barrier(BBB) permeability,the expression of tight junction proteins(TJPs) and the activity/expression of MMPs.RESULTS In the mice infused with tPA at 5 h post ischaemia,there were significant increases in mortality,brain infarction,brain oedema,brain haemoglobin level,neural apoptosis,Iba-1 staining(microglia activation) and myeloperoxidase staining(neutrophil infiltration).All these tPA-induced alterations were significantly prevented by NMN administration.Mechanistically,the delayed tPA treatment increased BBB permeability by downregulating TJPs,including claudin-1,occludin and zonula occludens-1,and enhancing the activities and protein expression of MMP9 and MMP2.Similarly,NMN administration partly blocked these tPAinduced molecular changes.CONCLUSION Our results demonstrate that NMN ameliorates tPAinduced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.展开更多
文摘目的探讨替罗非班治疗作为补充手段用于未接受静脉溶栓的急性缺血性脑卒中(AIS)患者机械取栓(MT)后静脉维持治疗的可行性与安全性。方法入选不符合静脉溶栓条件且CT血管成像证实为大动脉闭塞的87例AIS患者,其中MT+替罗非班维持(MT+T)组44例,MT组43例。MT+T组患者采用支架取栓并在术后立即静脉泵入0.1μg·kg-1·min-1替罗非班维持24 h,之后口服抗血小板聚集药物;MT组患者采用支架取栓治疗,术后口服抗血小板聚集药物。比较两组患者术前基线资料、血管再通情况、神经功能恢复情况、术后并发症及死亡情况。结果MT+T组与MT组患者术后14 d美国国立卫生研究院卒中量表(NIHSS)评分[(7.7±2.2)分vs.(8.8±3.3)分]、术后并发症[4.55%(2/44)vs.6.98%(3/43)]及病死率[2.27%(1/44)vs.2.33%(1/43)]比较,差异均无统计学意义(P均>0.05);而MT+T组患者术后90 d改良Rankin量表(mRS)评分低于MT组[(1.7±1.0)分vs.(2.2±1.1)分,t=2.479,P=0.015]。亚组分析显示,MT+T组取栓次数>3次的患者术后14 d NIHSS评分[(8.6±3.1)分vs.(12.5±3.5)分]及术后90 d mRS评分[(1.7±1.5)分vs.(2.8±1.0)分]均低于MT组(t=2.996、2.172,P=0.006、0.040);MT+T组及MT组取栓次数≤3次的患者术后14 d NIHSS评分[(7.4±1.6)分vs.(7.2±1.5)分]及术后90 d mRS评分[(1.7±0.7)分vs.(2.0±1.1)分]比较差异均无统计学意义(t=0.441、1.362,P=0.661、0.178)。结论替罗非班可作为未接受静脉溶栓的AIS患者行3次以上支架取栓治疗后的补充手段,可有效改善患者的神经功能及预后,且不增加脑出血转化风险。
基金supported by National Natural Science Foundation of China(8142204981473208+3 种基金816734858137341481130061) National 863 Plan Young Scientist Program of China(2015AA020943)
文摘OBJECTIVE Tissue plasminogen activator(tPA) is the only approved pharmaco.logical therapy for acute brain ischaemia;however,a major limitation of tPA is the haemorrhagic trans.formation that follows tPA treatment.Here,we determined whether nicotinamide mononucleotide(NMN),a key intermediate of nicotinamide adenine dinucleotide biosynthesis,affects tPA-induced haemorrhagic transformation.METHODS Middle cerebral artery occlusion(MCAO) was achieved in CD1 mice by introducing a filament to the left MCA for 5 h.When the filament was removed for reperfusion,tPA was infused via the tail vein.A single dose of NMN was injected i.p.(300 mg·kg^(-1)).Mice were killed at 24 h post ischaemia,and their brains were evaluated for brain infarction,oedema,haemoglobin content,apoptosis,neuroinflammation,blood-brain barrier(BBB) permeability,the expression of tight junction proteins(TJPs) and the activity/expression of MMPs.RESULTS In the mice infused with tPA at 5 h post ischaemia,there were significant increases in mortality,brain infarction,brain oedema,brain haemoglobin level,neural apoptosis,Iba-1 staining(microglia activation) and myeloperoxidase staining(neutrophil infiltration).All these tPA-induced alterations were significantly prevented by NMN administration.Mechanistically,the delayed tPA treatment increased BBB permeability by downregulating TJPs,including claudin-1,occludin and zonula occludens-1,and enhancing the activities and protein expression of MMP9 and MMP2.Similarly,NMN administration partly blocked these tPAinduced molecular changes.CONCLUSION Our results demonstrate that NMN ameliorates tPAinduced haemorrhagic transformation in brain ischaemia by maintaining the integrity of the BBB.
