类风湿关节炎患者血浆同型半胱氨酸水平与甲氨蝶呤和叶酸的作用效果

Level of homocysteine in patients with rheumatoid arthritis and the effects of methopterin and folic acid

目的:比较类风湿关节炎患者与健康者同型半胱氨酸水平,观察甲氨蝶呤及叶酸治疗对类风湿关节炎患者同型半胱氨酸水平和风湿性关节炎严重程度的影响。方法:①选择2002-03/2003-12在哈尔滨医科大学附属第一医院风湿免疫科住院的类风湿关节炎患者63例。均签署知情同意书。随机将63例类风湿关节炎患者分为2组:安慰剂对照组31例,叶酸治疗组32例。同期选择本院健康体检者40人为健康对照组。②两组均给予甲氨蝶呤治疗,10～20mg/次,1次/周。叶酸治疗组另外服用小剂量叶酸片,2.5mg/d,治疗3个月。安慰剂对照组患者另外服用安慰剂(淀粉制作),服用剂量及治疗时间同叶酸治疗组。③应用高效液相微柱层析法测定血浆同型半胱氨酸浓度。④采用疾病活动度积分作为治疗前后风湿性关节炎严重程度判定标准。结果:安慰剂对照组有2例失访,叶酸治疗组有2例出现无法耐受的胃肠道副反应停用甲氨蝶呤,1例失去随访,最终进入结果分析的类风湿关节炎患者58例,健康者40人。①血浆同型半胱氨酸水平:治疗前类风湿关节炎患者明显高于健康对照组犤(18.09±12.15),(13.24±5.72)μmol/L,P<0.05犦。安慰剂对照组治疗后明显高于治疗前犤(22.04±11.90),(17.45±15.9)μmol/L,P<0.05犦;叶酸治疗组治疗前后相近犤(18.44±12.51),(16.21±8.34)μmol/L,P>0.05犦。②疾病活动度积分:安慰剂对照组治疗后明显低于治疗前(4.18±0.63,5.76±0.92,P<0.01);叶酸治疗组治疗后明显低于治疗前(4.04±0.61,5.67±0.89,P<0.01);两组治疗后下降幅度相近。说明叶酸对甲氨蝶呤疗效无影响。结论:①类风湿关节炎患者普遍存在着高同型半胱氨酸血症,甲氨蝶呤的治疗会引起同型半胱氨酸的进一步增高。②小剂量(2.5mg/d)的叶酸补充能有效地降低甲氨蝶呤引起的高血浆同型半胱氨酸水平,而且不影响甲氨蝶呤的疗效。

AIM： To compare the levels of homocysteine between patients with rheumatoid arthritis and healthy people, and observe the influence of methopterin and folic acid on the level of homocysteine in the patients and the severity of rheumatoid arthritis. METHODS： ①Sixty-three inpatients with rheumatoid arthritis selected from the Department of Rheumatology and Immunology, the First Clinical Medical College, Harbin Medical University between March 2002 and December 2003 were randomly divided into placebo control group （n=31） and folic acid treated group （n=32）, another 40 healthy physical examinees in the hospital at the same period were taken as the healthy control group. ② All the patients were treated with methopterin, 10-20 mg for each time, once every week, and those in the folio acid treated group were given folic acid tablet of small dosage （2.5 mg per day） for 3 months, and those in the placebo control group took placebo, which was made of starch （2.5 mg per day） for 3 months. ③ The concentration of homocysteine in plasma was determined with the high performance liquid phase chromatography. ④The integra of disease activity was taken as the standard for evaluating the severity of rheumatoid arthritis before and after treatment. RESULTS： Two cases in the placebo control group lost to the follow-up, in the folic acid treated group, 2 cases stopped taking methopterin for the occurrence of intolerable gastrointestinal side effect, and 1 case lost to the follow-up; finally 58 patients with rheumatoid arthritis and 40 healthy people were involved in the analysis. ① The level of homocysteine in plasma： Before treatment, it was obviously higher in the patients with rheumatoid arthritis than in the healthy control group [（18.09±12.15）, （13.24±5.72） μmol/L, P 〈 0.05]. In the placebo control group, it wasobviously higher after treatment than before treatment [（22.04±11.90）, （17.45±15.9） μmol/L, P 〈 0.05. In the folic acid treated group, it was close before and after treatment [（18.44±12.51）, （16.21±8.34） μmol/L, P 〉 0.05]. ②The integra of disease activity： In the placebo control group, it was obviously lower after treatment than before treatment （4.18±0.63, 5.76±0.92, P 〈 0.01）. In the folie acid treated group, it was obviously lower after treatment than before treatment （4.04±0,61, 5.67±0.89,P 〈 0.01）. The decreased range hetween the two groups was close, indicating that folic acid had no influence on the effect of methopterin. CONCLUSION： Hyperhomoeysteinemia commonly exists in patients with rheumatoid arthritis, and the treatment of methopterin can result in the further increase of homocysteine. ② The folie acid supplementation of small dosage （2.5 mg per day） can effectively decrease the higher level of homocysteine in plasma caused by methopterin without affecting its effect.