法舒地尔对急性冠脉综合征患者相关血浆因子水平的影响

Effects of fasudil on levels of Correlation of plasma factor in patients with acute coronary syndrome

目的探讨法舒地尔对急性冠脉综合征(acute coronary syndrome,ACS)患者血浆hsCRP、ET-1、MMP-2和MMP-9水平的影响,了解法舒地尔对ACS患者粥样斑块的稳定作用。方法选择山东省济宁市第一人民医院收治的未接受冠状动脉介入治疗的ACS患者56例(ACS组),其中给予常规药物治疗28例(常规治疗组),给予法舒地尔治疗28例(法舒地尔组)。另择同期在院因不明原因胸痛行常规检查无异,并经冠状动脉造影检查无冠状动脉病变者22例作为正常对照组。常规治疗组和法舒地尔治疗组均应用相似剂量的阿司匹林、阿托伐他汀钙、单硝酸异山梨酯片及低分子肝素钙等治疗;法舒地尔组在此基础上再加行盐酸法舒地尔注射液(30 mg盐酸法舒地尔与100 ml 0.9%氯化钠溶液混合)静滴,2次/d。两组患者均治疗10 d。所有观察对象均采血检测高敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)、内皮素-1(endothelin-1,ET-1)、血清基质金属蛋白酶(matrix metalloproteinase,MMP)-2和MMP-9水平,并作各组间及治疗前后的比较。两组间及组内治疗前后hs-CRP、ET-1、MMP-2、MMP-9水平的比较均采用t检验。结果 ACS组治疗前hs-CRP、ET-1、MMP-2、MMP-9水平分别为(12.6±2.4)mg/L、(129±6)pg/ml、(66±13)ng/ml、(578±93)ng/ml,均显著高于正常对照组[(1.8±1.0)mg/L、(95±5)pg/ml、(21±9)ng/ml、(277±52)ng/ml],差异均有统计学意义(t=4.56、4.12、5.69、6.14,均P<0.01)。法舒地尔组及常规治疗组治疗后血浆hsCRP、ET-1、MMP-2、MMP-9水平分别为(4.0±2.3)mg/L、(107±8)pg/ml、(30±12)ng/ml、(197±43)ng/ml及(5.8±1.7)mg/L、(120±6)pg/ml、(39±9)ng/ml、(275±46)ng/ml,均显著低于治疗前[分别为(11.4±2.1)mg/L、(130±7)pg/ml、(63±12)ng/ml、(579±50)ng/ml及(11.7±2.2)mg/L、(132±7)pg/ml、(64±10)ng/ml、(574±85)ng/ml],差异均有统计学意义(t=6.28、4.17、5.43、6.85,5.63、4.88、5.16、6.37;均P<0.01)。治疗前两组hs-CRP、ET-1、MMP-2、MMP-9水平的差异均无统计学意义(t=0.65、0.43、0.29、0.76,均P>0.05);治疗后法舒地尔组血浆hs-CRP、ET-1、MMP-2、MMP-9水平均较常规治疗组显著降低,差异均有统计学意义(t=4.16、4.02、3.97、5.45,均P<0.01)。结论法舒地尔能降低ACS患者血浆hs-CRP、ET-1、MMP-2和MMP-9的水平,发挥稳定粥样斑块的作用。

Objective To investigate the effects of fasudil on hs-CRP, ET-1, MMP-2 and MMP-9 in patients with acute coronary syndrome (ACS) and to expore the effect of fasudil on plaque stability in&nbsp;ACS patients.MethodsFifty-six cases of acute myocardial infarction patients who were not receive given percutaneous coronary intervention were selected (ACS group). They were randomly divided into conventional therapy group (n=28) and fasudil treatment group (n=28). Twenty-two patients with stable angina pectoris (SAP) were selected as SAP group and 22 healthy people who were negative in CAG examination were selected as control group. The conventional therapy group and fasudil treatment group received similar doses of aspirin, atorvastatin, isosorbide 5-mononitrate and low molecular weight heparin calcium treatment. In addition, patients in fasudil group received fasudil (30 mg fasudil with 100 ml of 0.9% normal saline) iv bid. The duration of the treatment were 10 days in both groups. The levels of hs-CRP, ET-1, MMP-2 and MMP-9 in peripheral blood were evaluated at the beginning and the end of the treatment in all patients included. Studentt-test was applied to compare the difference of pre- and post-treatment hs-CRP, ET-1, MMP-2 and MMP-9 levels within and with different groups.ResultsThe peripheral blood levels of hs-CRP, ET-1, MMP-2 and MMP-9 in ACS group at the beginning of treatment were (12.6±2.4) mg/L, (129±6) pg/ml, (66±13) ng/ml, and (578±93) ng/ml. They were all significantly higher than the control group [(1.8±1.0) mg/L, (95±5) pg/ml, (21±9) ng/ml, and (277±52) ng/ml] witht values of 4.56, 4.12, 5.69, and 6.14 respectively (P<0.01).The endpoint hs-CRP, ET-1, MMP-2 and MMP-9 in fasudil group and conventional treatment group were (4.0±2.3) mg/L, (107±8) pg/ml, (30±12) ng/ml, (197±43) ng/ml and (5.8±1.7) mg/L, (120±6) pg/ml, (39±9) ng/ml, (275±46) ng/ml, respectively, which were all decreased compared with pre-treatment levels [(11.4±2.1) mg/L, (130±7) pg/ml, (63±12) ng/ml, (579±50) ng/ml and (11.7±2.2) mg/L, (132±7) pg/ml, (64±10) ng/ml, (574±85) ng/ml, respectively], witht=6.28, 4.17, 5.43, 6.85, 5.63, 4.88, 5.16, 6.37 andP<0.01. No difference of pre-treatment hs-CRP, ET-1, MMP-2 and MMP-9 levels between groups (t=0.65, 0.43, 0.29, 0.76, andP>0.05). The post-treatment hs-CRP, ET-1, MMP-2 and MMP-9 levels in fasudil group were signiifcantly reduced compared with conventional group (t=4.16, 4.02, 3.97, 5.45 andP<0.01).ConclusionFasudil can reduce plasma levels of hs-CRP, ET-1, MMP-2 and MMP-9 in ACS patients. This may play a role in plaque stability in patients with ACS.