痹肿消汤对活动期类风湿关节炎患者血清基质金属蛋白酶3及其组织抑制剂1的影响

Effects of bizhongxiao decoction on serum matrix metalloproteinase 3 and its tissue inhibitors of metalloproteinase 1 in patients with rheumatoid arthritis at active phase

目的:观察从分子生物学水平痹肿消汤对活动期类风湿性关节炎患者血清基质金属蛋白酶3及其组织抑制剂1的影响及其治疗作用。方法:52例活动期类风湿性关节炎患者均来自2003-06/2004-06中南大学湘雅医院。随机分为痹肿消汤治疗组(简称中药组,n=27),用痹肿消汤治疗,1剂/d,水煎服2次。甲氨喋呤+柳氮磺嘧啶治疗组(简称对照组,n=25),甲氨喋呤起始量7.5mg口服,1次/周,逐渐加量至15mg,1次/周;同时配以等量叶酸口服。柳氮磺嘧啶起始量0.25g口服,3次/d,逐渐加量至0.5g,3次/d。上述两组均治疗3个月为1个疗程,于治疗前和治疗3个月后分别检测血清基质金属蛋白酶3,金属蛋白酶组织抑制剂1水平,计算两者比值。结果:按实际处理分析,中药组有2例失访,3例未能坚持完疗程而脱落,对照组有3例失访,3例出现副反应而脱落。①治疗3个月后,中药组患者(n=22)血清基质金属蛋白酶3、金属蛋白酶组织抑制剂1及两者的比值较治疗前明显降低(52.17±23.19)μg/L,(320.48±101.16)μg/L,0.190±0.118;(93.01±41.42)μg/L,(461.80±132.27)μg/L,0.227±0.132,t=6.166,8.369,2.589,P<0.01或P<0.05。②与对照组(n=19)治疗后比较基本相似(49.91±22.34)μg/L,(317.21±93.87)μg/L,0.184±0.118,P>0.05。

AIM: To observe the effects of bizhongxiao decoction from the molecular biological level on matrix metalloproteinase 3(MMP-3) and its tissue inhibitors of metalloproteinase 1(TIMP-1) in patients with rheumatoid arthritis (RA) at active phase,and study its curative effects. METHODS:Fifty-two RA patients at active phase,who were from Xiangya Hospital of Central South University between June 2003 and June 2004,were randomly divided into bizhongxiao decoction treated group [traditional Chinese medicine(TCM) group,n=27] and methotrexate (MTX) +sulfasalazine salicylazosulfapyridine (SASP) (control group,n=25).Patients in the TCM group were treated with bizhongxiao decoction,which was decocted with water for twice,one dose per day.In the control group,the initial dose of oral MTX was 7.5 mg,once a week,and it was gradually added to 15 mg,once a week;Meanwhile,oral folic acid of the same dose was also taken;The initial dose of oral SASP was 0.25 g,three times a day,and it was added gradually to 0.5 g,three times a day.All the patients in both groups were treated for three months as a course.The serum concentrations of MMP-3 and TIMP-1 were tested and the ratio of MMP-3 to TIMP-1 was calculated before and after the 3-month treatment. RESULTS:According to analysis of actual treatment,2 cases lost to follow-up and 3 cases missed for did not finish the course in the TCM group;3 cases lost to follow-up and 3 cases missed for the occurrence of side effects in the control group. ①After the 3-month treatment, the serum concentrations of MMP-3 and TIMP-1 and the ratio of MMP-3 to TIMP-1 in the TCM group(n=22) [(52.17±23.19) μg/L, (320.48±101.16) μg/L,0.190 ±0.118] were decreased obviously as compared with those before treatment [(93.01±41.42) μg/L, (461.80±132.27) μg/L,0.227±0.132] (t=6.166, 8.369, 2.589, P< 0.01 or P< 0.05). ②After treatment, there were no significant differences between the TCM group and control group[(49.91±22.34) μg/L,(317.21±93.87) μg/L,0.184±0.118] (P >0.05). CONCLUSION:Bizhongxiao decoction can regulate the disturbance of serum MMP-3 and TIMP-1 balances, and then rebuild the stability of organs, and relieve the matrix degradation and destruction of bone, so as to treat RA, the changes of experimental data are similar to those of MTX combined with SASP.