PAS三联疗法对急性脑梗死患者血清MMP-7、MMP-8水平的影响及颈动脉易损斑块的干预作用

Effect of PAS Triple Therapy on Serum Marix Metalloproteinase-7,-8 and Atherosclerosis in Patients with Acute Cerebral Infarction

目的:探讨普罗布考、阿司匹林、他汀类药物(PAS)三联疗法对急性脑梗死患者血清超敏C-反应蛋白(hs-CRP)、基质金属蛋白酶-7(MMP-7)及基质金属蛋白酶-8(MMP-8)水平的影响,观察其对颈动脉易损斑块的干预作用。方法:135例急性脑梗死患者根据颈动脉超声检查结果分为颈动脉稳定斑块组(n=45)和颈动脉易损斑块组(n=90)。将稳定斑块组作为对照组,易损斑块组根据治疗方法按随机数字法分为AS组45例(阿司匹林100mg/d,阿托伐他汀20mg/d,口服)和PAS组45例(阿司匹林100mg/d,阿托伐他汀20mg/d,普罗布考0.25/次,2次/d,口服)。比较治疗前和治疗4周血清hs-CRP、MMP-7和MMP-8水平;观察治疗前及治疗后12月颈动脉内-中膜厚度(IMT值)、斑块面积及斑块回声变化。结果:治疗前,易损斑块组中两亚组(AS组和PAS组)血清hs-CRP、MMP-7和MMP-8水平均高于稳定斑块组(对照组),差异有显著性(P均<0.01);两组(AS组和PAS组)间血清hs-CRP、MMP-7和MMP-8水平差异无显著性(均P>0.05)。治疗后4周,PAS组中血清hs-CRP、MMP-7和MMP-8水平均低于AS组,其下降幅度均大于AS组,差异具有显著性(P均<0.01);治疗12月后,两组IMT值和斑块面积较治疗前减少,且PAS组两项指标低于AS组,差异具有显著性(P均<0.01);PAS组低回声斑块回声增强例数多于AS组(P<0.01)。结论:PAS三联疗法能迅速降低脑梗死患者血清炎性因子水平,具有更强的抗炎作用,可逆转和稳定斑块。

Objective： To observe the influence of combination therapy of probucol,aspirin and statins drugs（PAS） on inflammatory factors such as high sensitivity C-reactive protein（hs-CRP）,marix metalloproteinase-7（MMP-7） and marix metalloproteinase-8（MMP-8） in patients with acute cerebral infarction（ACI） and its effect on the role of carotid artery plaque.Methods： According to the results of carotid artery ultrasound,135 cases of patients with ACI were divided into carotid stable plaque group（n=45） and carotid vulnerable plaque group（n=90）.Stable plaque group was considered as control group.Ninety cases with carotid vulnerable plaque were randomly divided into aspirin and statins drugs（AS） group（n=45,aspirin 100 mg/d and atorvastatin 20 mg/d,orally） and PAS group（n=45,aspirin 100 mg/d,atorvastatin 20 mg/d,and probucol 0.25 g,b.i.d.,orally）.Serum hs-CRP,MMP-7,and MMP-8 levels were detected in all patients before treatment and four weeks after treatment.The intima-media thickness（IMT）,plaque area and echogenicity of carotid plaques in all cases were evaluated by Doppler ultrasonography during a 12-month follow-up period.Results： Before treatment,serum hs-CRP,MMP-7,and MMP-8 levels in two subgroups of vulnerable plaque group（AS group and PAS group） were higher than that in stable plaque group（control group）（all P0.01）,while no significant differences were observed between AS group and PAS group（all P0.05）.Levels of hs-CRP,MMP-7 and MMP-8 decreased significantly in AS group after 4 weeks,as well as in PAS group（all P0.01）.Four weeks later,the hs-CRP,MMP-7 and MMP-8 levels were obviously higher in PAS group than in AS group（all P0.01）.Whether in AS or PAS group,significant increase in echogenicity of carotid plaques and decrease in plaque area and IMT were noted after therapy.However,the value of IMT and plaque area were significantly less in PAS group as compared to AS group（both P0.01）.The cases with increasing hypoechoic plaques were significantly more in PAS group after treatment than in AS group（P0.01）.Conclusion： Combination therapy of probucol,aspirin and statins drugs could rapidly reduce serum inflammatory factors in patients with ACI,and might have stronger anti-inflammation function,so as to reverse or stabilize the atherosclerosis plaque.