糖皮质激素对多发性硬化患者血清MMP-9、TIMP-1水平的调控作用

目的观察糖皮质激素(GC)治疗多发性硬化(MS)患者过程中血清MMP-9和TIMP-1水平的动态变化,探讨GC治疗MS的作用机制。方法收集80例MS患者不同时间点外周血;急性初期进行EDSS评分,根据EDSS评分将MS患者分为2组,其中GC治疗组(EDSS≧5分)急性期50例、追踪至缓解期46例,空白对照组(EDSS<5分)急性期30例、缓解期26例;健康对照组50例。采用酶联免疫吸附试验法检测血清MMP-9与TIMP-1水平。结果 (1)急性期MS血清MMP-9水平高于缓解期和健康对照组,而TIMP-1水平降低(P<0.05),缓解期和健康对照组间差异无统计学意义(P>0.05)。(2)MMP-9在MS血清中呈先升后降的趋势;GC治疗组不同时间点间差异有统计学意义(F=16.35,P<0.01),治疗1w时MMP-9水平达高峰,治疗4w时较治疗前降低(P<0.05);而空白对照组发病2w时MMP-9水平达高峰,且高于GC治疗组高峰(P<0.05)。(3)GC治疗组TIMP-1水平呈缓慢增高趋势,不同时间点间差异有统计学意义(F=4.27,P<0.05),与治疗前相比,治疗4w时TIMP-1水平升高(P<0.05);而空白对照组TIMP-1水平随病情波动变化不大。结论 MMP-9在MS急性期血清中表达增强,TIMP-1表达降低,MMP-9、MMP-9/TIMP-1水平反应了MS疾病活动性,监测其水平具有一定的诊断价值;MMP-9在MS血清中呈先升后降趋势,GC治疗可降低MMP-9上升的幅度,缩短MMP-9升高的时间,降低MMP-9的表达,并诱导TIMP-1的表达,这可能是GC治疗MS、加速MS病情缓解、缩短其病程的机制之一。

Glucocorticoid' s regulation on MMP-9 and TIMP-1 serum levels of patients with multiple sclerosis

Objective To observe glucocorticoid’s regulation on matrix metalloproteinase-9(MMP-9)and tissue inhibitor of matrix metalloproteinase-1(TIMP-1)serum levels of patients with multiple sclerosis(MS),and to explore the mechanism of glucocorticoid(GC)therapy for MS.Methods 80 acute MS patients and 50 healthy controls were enrolled in the study.Acute MS initial clinical status were evaluated with the Expanded Disability Status Scale(EDSS).Acute MS was divided into 2 groups according to EDSS,one was GC treated group with EDSS≧5,including 50 acute MS patients,among them,46 cases were followed-up in the remission;and blank group with EDSS<5,including 30 acute MS patients,among them,26 were followed-up in the remission.The serum of MS patients in different time and healthy controls on admission were performed.The concentration of MMP-9 and TIMP-1 was determined by enzyme-linked immunoassay.Results The MMP-9 serum level of acute MS was significantly higher than that of the remission MS and healthy controls(P<0.01),while TIMP-1 level was a little lower(P<0.05).There was no obvious statistical significance between the remission MS and the health controls(P>0.05).The MMP-9 serum level first increased and then descended in MS.There was statistical significance between different time during GC therapy for MS(F=16.35,P<0.01).The MMP-9 peak was achieved in the first week,and MMP-9 level in the forth week was lower than that of before GC treatment;yet the MMP-9 peak of blank group was achieved in the second week and higher than that of GC treatment group(P<0.05).During GC therapy for MS,the TIMP-1 level assumed the slow increased trend with statistical significance(F=4.27,P<0.05).The TIMP-1 level in the forth week was higher than that of before treatment(P<0.05),yet the TIMP-1 level of the blank group had hardly any change along with state evolution of MS.Conclusion The MMP-9 level elevates and TIMP-1 level reduces in the acute MS.The MMP-9 serum level and MMP-9 to TIMP-1 ratio may be a biomarker that reflects the activity of disease,and detecting their levels has certain diagnosis value.The MMP-9 serum level first increases and then descends in MS.GC suppresses MMP-9 expression,raises TIMP-1 level in acute MS,inhibits MMP-9 growth range,and shortens MMP-9 growth time which may be one of the main mechanisms of GC therapy for MS to improve the clinical symptoms and shorten the course of acute MS.