盐酸替罗非班对急性进展性脑梗死脑灌注及MMP-9影响的系列研究Ⅱ

Series study II on the effect of tirofiban hydrochloride on cerebral perfusion and MMP-9 in patients with acute progressive cerebral infarction

目的研究盐酸替罗非班对急性进展性脑梗死(APCI)脑灌注及血清基质金属蛋白-9(MMP-9)的影响,为APCI的治疗提供参考。方法纳入2019-01-2023-05新郑市公立人民医院住院的APCI患者132例为研究对象,随机分为A组(61例)和B组(61例);B组应用肠溶阿司匹林100 mg/d、氢氯吡格雷75 mg/d、阿托伐他汀钙40 mg/d等常规治疗,A组在入院时持续静脉泵入盐酸替罗非班代替肠溶阿司匹林和氢氯吡格雷,治疗前30 min内0.4μg·kg^(-1)·min^(-1)静脉泵入,之后以0.1μg·kg^(-1)·min^(-1)持续泵入,治疗至44 h复查头CT排除脑出血后加用肠溶阿司匹林和氢氯吡格雷,治疗48 h后停用盐酸替罗非班,其余治疗同B组。2组均在入院时及治疗后48 h行3.0T高场强磁共振脑灌注检查,以梗死区局部脑血容量(rCBV)、局部脑血流量(rCBF)、平均通过时间(MTT)、达峰时间(TTP)评价脑灌注效果,同时抽取外周静脉血检测MMP-9浓度。结果A组治疗前MTT(4.45±1.03)s,TTP(11.52±2.19)s,治疗48 h后MTT(2.06±1.41)s,TTP(8.17±2.01)s,均较治疗前明显缩短(P<0.05);治疗前rCBV(18.15±8.14)mL,rCBF(3.86±0.77)mL/min,治疗48 h后rCBV(37.42±6.17)mL,rCBF(8.18±0.51)mL,均较治疗前明显增加(P<0.05);治疗前血清MMP-9水平(205.04±41.15)μg/L,治疗48 h后为(158.22±62.07)μg/L,较治疗前明显下降(P<0.05)。B组治疗前MTT(4.84±1.73)s,TTP(12.06±2.33)s,治疗48 h后MTT(3.74±1.25)s,TTP(10.93±1.62)s,均较治疗前明显缩短(P<0.05);治疗前rCBV(18.04±7.25)mL,rCBF(3.91±0.63)mL/min,治疗48 h后rCBV(25.81±6.09)mL,rCBF(5.76±0.82)mL/min,均较治疗前明显增加(P<0.05);治疗前血清MMP-9水平(198.82±40.95)μg/L,治疗48 h后为(176.35±51.79)μg/L,较治疗前明显下降(P<0.05)。治疗48 h后A组和B组相比,MTT和TTP均明显缩短,rCBV和rCBF均明显增加,差异均有统计学意义(P<0.05)。治疗48 h后A组血清MMP-9较B组下降更明显(t=15.07,P<0.05)。结论盐酸替罗非班可显著改善APCI患者脑灌注、降低血清MMP-9水平,明显减轻APCI患者脑组织损伤,疗效优于传统疗法。

Objective To investigate the effect of tirofiban hydrochloride on cerebral perfusion and serum matrix metalloproteinase-9(MMP-9)in patients with acute progressive cerebral infarction(APCI)and provide reference for the treatment of APCI.Methods A total of 132 APCI patients admitted to Xinzheng Public People’s Hospital from January 2019 to May 2023 were included as the study subjects and were randomly divided into Group A(61 cases)and Group B(61 cases).Group B received conventional treatment including enteric-coated aspirin 100 mg/d,clopidogrel 75 mg/d,and atorvastatin calcium 40 mg/d.After admission,group A received tirofiban hydrochloride by means of intravenous infusion continuously instead of enteric-coated aspirin and clopidogrel treatment at the rate of 0.4 μg·kg^(-1)·min^(-1) for 30 minutes,and then at rate of 0.1 μg·kg^(-1)·min^(-1) for 48 hours,and then added enteric-coated aspirin and clopidogrel at 44 hours after excluding cerebral hemorrhage by CT,with the remaining treatment the same as Group B.Both groups underwent 3.0T high-field magnetic resonance perfusion imaging of the brain at admission and 48 hours after exacerbation to evaluate the cerebral perfusion effects,including regional cerebral blood volume(rCBV),regional cerebral blood flow(rCBF),mean transit time(MTT),and time to peak(TTP).Peripheral venous blood samples were collected to measure MMP-9 concentration.Results Group A:before treatment,MTT was(4.45±1.03)s,TTP was(11.52±2.19)s,after treatment for 48 hours,MTT was(2.06±1.41)s,TTP was(8.17±2.01)s,both are shorter than those before treatment obviously(P<0.05).Before treatment,rCBV was(18.15±8.14)mL,rCBF was(3.86±0.77)mL/min,after treatment for 48 hours,rCBV was(37.42±6.17)mL,rCBF was(8.18±0.51)mL,both increased than those before treatment obviously(P<0.05).Before treatment,serum MMP-9 was(205.04±41.15)μg/L,after treatment for 48 hours,serum MMP-9 was(158.22±62.07)μg/L,which decreased obviously compared with those before treatment(P<0.05).Group B:before treatment,MTT was(4.84±1.73)s,TTP was(12.06±2.33)s,after treatment for 48 hours,MTT was(3.74±1.25)s,TTP was(10.93±1.62)s,both are shorter than those before treatment obviously.Before treatment,rCBV was(18.04±7.25)mL,rCBF was(3.91±0.63)mL/min,after treatment for 48 hours,rCBV was(25.81±6.09)mL,rCBF was(5.76±0.82)mL,both increased than those before treatment obviously(P<0.05).Before treatment,serum MMP-9 was(198.82±40.95)μg/L,after treatment for 48 hours,serum MMP-9 was(176.35±51.79)μg/L,which decreased obviously compared with those before treatment(P<0.05).After 48 hours of treatment,Group A showed significantly shorter of MTT and TTP compared to Group B(P<0.05),while CBV and CBF in Group A were significantly higher than those in Group B(P<0.05).After 48 hours of treatment,the serum MMP-9 levels in group A decreased significantly compared to Group B(t=15.07,P<0.05).Conclusion Tirofiban hydrochloride can improve cerebral perfusion and reduce serum MMP-9 levels significantly in APCI patients,thereby reducing brain tissue damage in APCI patients,and its efficacy is superior to conventional therapy.