冠状动脉内注射负荷量替罗非班对急性心肌梗死患者心肌灌注及心功能的影响

目的：探讨急性ST段抬高型心肌梗死（STEMI）患者急诊经皮冠状动脉注射负荷量盐酸替罗非班对心肌灌注及心功能的影响。方法：选择急性ST段抬高型心肌梗死患者270倒,随机分为实验组（n=133）和对照组（n=137）。所有入选患者均急诊进行经皮冠状动脉介入治疗（PCI）,术中实验组患者予冠脉内注射负荷量盐酸替罗非班,对照组不予注射,主要终点为观察PCI术后即刻造影结果,同时观察术后3天、30天、360天的左室射血分数（EF）,左室舒张末期内径（LVEDD）、左室收缩期末内径（LVESD）及术后360天主要心血管不良事件的发生率;次要终点为一般出血事件的发生率、血小板下降情况、血小板聚集率的变化。结果：实验组患者术后校正的TIMI帧数、术后2小时ST段回落程度、磷酸肌酸肌酶同工酶（CK-MB）峰值及峰值时间显著优于对照组（P〈0．05）．梗死相关血管无复流发生率及360天MACE的发生率显著低于对照组（P〈0．05）,与对照组相比,术后30天、360天的EF值明显增加,术后30天、360天的LVEDD、LVESD显著降低（P〈0．05）;实验组术后2天血小板聚集率明显低于对照组（P〈0．05）。结论：急诊PCI术中联合冠脉内注射负荷量替罗非班可以改善心肌灌注水平及心功能,且不增加出血事件的发生率,提高远期愈后。     

Collagen XVII promotes integrin-mediated squamous cell carcinoma transmigration--a novel role for alphaIIb integrin and tirofiban

The expression of collagen XVII (BP180), a transmembrane hemidesmosomal component, is upregulated in invasive areas of epithelial tumors. The collagenous ectodomain of collagen XVII is cleaved from the plasma membrane of keratinocytes and malignant epithelial cells. The released ectodomain is predicted to regulate cell detachment, differentiation, and motility. We report that the cell adhesion domain of collagen XVII, Col15, is able to chemotactically attract invasive HSC-3 SCC cells but not keratinocytes. Analysis of integrin expression revealed that HSC-3 cells, unlike keratinocytes, express alphaIIb integrin, a platelet-specific fibrinogen receptor. We show that this novel chemotactic function is mediated by the known Col15-binding integrins alpha5beta1 and alphav and the platelet integrin alphaIIb. Moreover, we report that tirofiban, a FDA-proved alphaIIb integrin-blocking drug widely used for the therapy of acute coronary ischaemic syndrome and the prevention of thrombotic complications, inhibits the Col15 chemotaxis of HSC-3 carcinoma cells. Together, these data demonstrate a novel interaction between collagen XVII and alphaIIb integrin and also suggest a possibility to use tirofiban to inhibit the invasion and progression of alphaIIb expressing SCC tumors.     

经血栓抽吸导管应用替罗非班及硝普钠对急性前壁ST段抬高型心肌梗死患者急诊PCI治疗效果的影响

目的:探讨经血栓抽吸导管应用替罗非班及硝普钠对急性前壁ST段抬高型心肌梗死患者急诊经皮冠状动脉介入(PCI)治疗效果的影响。方法:选取2013年5月～2018年5月期间我院收治的急性前壁ST段抬高型心肌梗死患者80例,根据随机数字表法分为对照组(n=40,血栓抽吸术后行PCI治疗)和研究组(n=40,血栓抽吸术后,经导管注入替罗非班及硝普钠后再行PCI治疗),比较两组患者心电图ST段回落变化、心肌梗死溶栓治疗(TIMI)血流分级情况、心功能指标及不良心血管事件发生率。结果:研究组完全回落发生率高于对照组(P0.05);两组部分回落、无回落发生率比较差异无统计学意义(P0.05)。对照组PCI术后TIMI血流分级为3级的例数少于研究组(P0.05)。两组患者术后7 d左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)降低,且研究组低于对照组(P0.05);左室射血分数(LVEF)升高,且研究组高于对照组(P0.05)。术后6个月内研究组不良心血管事件总发生率为7.50%(3/40),低于对照组的25.00%(10/40)(P0.05)。结论:急性前壁ST段抬高型心肌梗死患者经血栓抽吸导管应用替罗非班及硝普钠后行PCI,可提高心功能、心肌灌注状态及心电图ST段完全回落率,并减少不良心血管事件的发生率。     

Characterization and metal affinity of Tirofiban, a pharmaceutical compound used in acute coronary syndromes

The crystal and molecular structure of Tirofiban [N-(n-butanesulfonyl)-O-(4-(4-piperidinyl)-butyl)-(S)-tyrosine] is here reported. In the solid state the carboxylic group is in the anionic form while the piperidine molecule appear in the protonated form. By H NMR spectroscopy and potentiometric study three pKa are found: pKa(COOH) = 3.1 (1), pKa(NHPIP) = 11.6(1) and pKa(NHSO2) = 13.8(1). The complexing ability of Tirofiban towards various metal ions (Cu(II), Ni(II), Co(II), Cd(II), Pb(II), Zn(II) and Ca(II)) is also determined by means of potentiometric studies. The prevailing species are [M(TirH)2]2+ where the ligand coordinates the metal ion through carboxylic group, while the piperidine nitrogen is still protonated. The great stability of these complexes may be due to the presence of hydrogen bond interactions, as well as the formation of stacking interactions involving the phenyl ring of the tyrosine residue.     

替罗非班联合尼可地尔对急诊PCI患者心功能和短期预后的影响

目的:探讨急诊PCI患者在联合使用替罗非班和尼可地尔后对心功能和短期预后的影响。方法:入选98例接受急诊PCI的AMI患者随机分为对照组(n=49)和联合治疗组(n=49)。对照组单纯给予替罗非班治疗,联合治疗组在对照组基础上给予尼可地尔5 mg tid口服治疗。观察记录两组患者治疗8周前后LVEF、NT-pro BNP水平,并随访MACE事件发生情况。结果:两组患者在治疗前LVEF及NT-pro BNP水平比较没有统计学差异(P0.05)。在治疗8周后联合治疗组和对照组LVEF及NT-pro BNP水平均较治疗前水平明显改善(P0.05)。治疗8周后联合治疗组患者LVEF及NT-pro BNP水平明显优于对照组患者(P0.05)。经过8周的治疗,联合治疗组再次发生心绞痛事件(6.12%VS 24.49%,P=0.025)、恶性心律失常(2.04%VS 16.33%,P=0.036)和心力衰竭事件(2.04%VS 18.37%,P=0.020)明显低于对照组。结论:替罗非班联合尼可地尔可进一步改善急诊PCI患者心功能及短期预后,值得临床推广。     

替罗非班联合丁苯酞治疗超时间窗急性脑梗死患者对血清HO-1、NO、VEGF、Ang-1的影响

摘要 目的：探讨替罗非班联合丁苯酞治疗超时间窗急性脑梗死患者对血清血红素加氧酶-1（HO-1）、一氧化氮（NO）、血管生成素-1（Ang-1）、血管内皮生长因子（VEGF）的影响。方法：选择2018年1月到2020年1月在我院接受治疗的141例超时间窗急性脑梗死患者,采用随机数表法分为联合组（n=71）和单药组（n=70）。单药组给予丁苯酞治疗,联合组在单药组的基础上给予替罗非班治疗。比较两组临床疗效、HO-1、NO、VEGF、Ang-1、美国国立卫生研究院卒中量表（NIHSS）、Barthel指数（Barthel）、凝血酶时间(TT)、凝血酶原时间(PT)、纤维蛋白原（FIB）水平变化情况及药物并发症发生情况。结果：治疗后,两组总有效率比较差异显著（P<0.05）;治疗前,联合组和单药组血清HO-1、NO、VEGF、Ang-1比较无显著差异;治疗后联合组和单药组血清HO-1、NO、VEGF随着时间的推移而降低,且联合组均低于单药组,Ang-1随着时间的推移而升高,且联合组均高于单药组,差异显著（P<0.05）;治疗前,联合组和单药组NIHSS、Barthel比较无显著差异;治疗后联合组和单药组NIHSS随着时间的推移而降低,且联合组均低于单药组,Barthel随着时间的推移而升高,且联合组均高于单药组,差异显著（P<0.05）。结论：在超时间窗急性脑梗死患者中应用替罗非班联合丁苯酞效果显著,可能与其可有效改善血清HO-1、NO、VEGF、Ang-1水平有关,且不增加不良反应。