| Background and ObjectivesMultiple sclerosis (MS) is a demyelinating disease characterized as multiple lesions and the remitting relapsing courses, recent studies have shown that autoimmunity may be the main pathogenic mechanism.the BBB damage and abnormal activated T lymphocyte into the central nervous system through the BBB are the first step of the development of multiple sclerosis,T lymphocyte into the central nervous system needs lots of factors,among which the matrix metalloproteinases play a key role, especially MMP-9 has a close relationship to the BBB damage and T lymphocyte into the central nervous system, and tissue inhibitor of metalloproteinase (TIMPs) are endogenous inhibitors of MMPs, which are multifunctional factors to inhibit MMPs activity. Different TIMPs don’t have high selectivity to MMPs, but TIMP-1 may specially be bind to MMP-9, which form reversible soluble complex of 1:1 ratio to inhibit MMPs. This paper mainly observed the dynamic changes of the serum MMP-9 and TIMP-1 level in the process of glucocorticoid treatment for patients with Multiple Sclerosis and explored the mechanism of glucocorticoid therapy for MS,looking for the new clues for MS treatment. Material and Methods80 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 patients was divided into 2 groups according to EDSS, one was GC treated group with EDSS≥5 including 48 acute MS patients (age: 35.5±13.0, range 15 to 58 years, disease course:3.5 years, range 3 months to 9 years), 45 of follow-up in the remission(2 patients relapsing and lpatient losing in follow-up) and another was blank group with EDSS< 5 including 22 acute MS patients (age: 31.2±14.0, range 18 to 55 years),18 of follow-up in the remission, because 3 patients relapsed and lpatient lost in follow-up. Fifty healthy volunteers (age:36.3±14.3, range 19 to 50 years) constituted healthy control group,which matched sex and age with MS groups. All MS patients came from MS patients in the neurology department of the frist affiliated hospital of ZhengZhou university from 2009 to 2011 and were diagnosed according to the McDonald’s creteria, all of them were laboratory-supported defined or clinical defined MS. Acute MS patients of GC treated group is given intravenous methylprednisolone(1000g/day) and nueral nutrition drug while the blank group is only given nueral nutrition drug, no steroids. The steroids are gradually decreased half quantity every 3 days until 4mg/day to take 3 consecutive days, the therapy course is about 4 weeks, oral steroids after 12 days. All subjects had no steroids and immune suppressant 3 months before recruiting and no other autoimmune diseases and infectious disease. They were well informed of all experimental purposes and signed a consent form.All MS patients were drown peripheral venous blood 3 ML in the initial phase, first week, second week, forth week of acute phase and the remission, healthy controls on the admission. The blood samples were preserved at the temperature-80℃. The sandwich-type ELISA was used to determine serum MMP-9 and TIMP-1 levels. The expression of the Statistical analysis results were meantstandard deviation(x±s), and the data was analyzed with spss 17.0 statistical software. Repeated measures ANOVA test was used to compare different groups, the two-two comparison between two groups was LSD test, the comparison between two independent sample is T test, EDSS points were compared with Wilcoxon rank test, and all the significant level was set at P<0.05.Results1. The MMP-9 serum levels of acute MS were significantly higher than that of the remission MS and healthy controls (P< 0.01) while TIMP-1 levels were a little lower than that of the remission MS and healthy controls (P< 0.05),they between the remission MS and the health controls had no obvious statistical significance (P> 0.05).2. 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=16.36, P < 0.01), compared with the MMP-9 serum level of the initial acute MS, that after the GC treatment in the first week achieved the peak (P< 0.01), that in the second week dropped to the basal level (P> 0.05), the MMP-9 serum level in the forth week of GC treatment was lower than that of the initial phase (P< 0.05). Yet the MMP-9 serum level of the blank MS group achieved the peak in the second week and was higher than that of GC treated group, and the MMP-9 level in the forth week was close to the initial level (P> 0.05).3. The TIMP-1 level assumed the slow increased trend in GC treated group, that of different time had statistical significance (F=6.45, P< 0.01). The TIMP-1 level in the forth week of GC treatment was higher than that of the initial phase, yet there was no statistical significance (P> 0.05) between in the first week and the forth week of the blank MS group.Conclusions1. The MMP-9 level elevates and the TIMP-1 level reduces in the acute MS, the MMP-9 serum level and the MMP-9/TIMP-1 ratio may be a biomarker reflecting the activity of the MS disease, and detecting their levels have certain diagnosis value.2. The MMP-9 serum level first increases and then descends in acute MS while the TIMP-1 level slowly increases.the GC therapy for MS inhibits the MMP-9 growth range and shortens the MMP-9 growth time, and lowers the MMP-9 level while induces the TIMP-1 transcripition, which is one of the mechanisms of GC speeding up the remission of the MS clinical symptoms and shorten the course of the acute phase of MS.3. The effects of GC on expression of MMP-9 and TIMP-1 are reciprocal, suppressing the MMP-9 expression and raising the level of TIMP-1, which may be one of the main mechanisms of GC treated MS patients.and the advantages of the GC treated MS makes us to infer the specific GC receptor agonists may be a reliable and new therapy drug for MS. |
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