甲氨蝶呤对类风湿关节炎患者骨破坏抑制及血清IL-1β和TNF-α的影响
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摘要
目的探讨甲氨蝶呤对类风湿关节炎患者骨破坏抑制及血清IL-1β、TNF-α的影响。方法选择2014年2月至2016年2月收治的类风湿关节炎患者60例进行回顾性分析,采用系统随机的方法分为对照组和观察组,每组30例。对照组采用来氟米特治疗,观察组患者采用用甲氨蝶呤治疗。观察2组患者临床疗效及不良反应发生情况,观察2组患者治疗前后的各项实验室检查指标及关节滑膜细胞培养液上清液中IL-1β、TNF-α及MMP-3指标水平及DAS28评分。结果观察组患者总有效率为90. 00%高于对照组的64. 52%,差异有统计学意义(P <0. 05)。治疗前,2组患者关节肿胀数、关节压痛数及ESR、CRP指标水平比较,差异无统计学意义(P> 0. 05)。治疗后,观察组的关节肿胀数及关节压痛明显少于对照组(P <0. 05);且观察组ESR及CRP指标明显低于对照组(P <0. 05)。治疗前,2组患者细胞培养液上清液中IL-1β、TNF-α及MMP-3指标水平比较差异无统计学意义(P> 0. 05)。治疗后,观察组的细胞培养液上清液中IL-1β、TNF-α及MMP-3指标水平明显低于对照组患者(P <0. 05)。2组患者治疗前DAS28评分比较无显著性差异(P> 0. 05)。2组患者治疗后DAS28评分较治疗前显著下降(P <0. 05),且观察组患者DAS28评分明显低于对照组(P <0. 05)。2组不良反应的发生情况比较无明显差异(P> 0. 05)。结论甲氨蝶呤治疗类风湿关节炎临床疗效显著,改善患者关节肿胀数及关节压痛数及ESR、CRP指标水平,并通过改善患者关节滑膜细胞中IL-1β、TNF-α及MMP-3指标水平,从而达到抑制骨破坏及改善DAS28评分的作用,且药物安全性高。
Objective To investigate the effects of methotrexate on inhibition of bone destruction,serum IL-1β and TNF-α in patients with rheumatoid arthritis( RA). Methods Clinical data of sixty patients with RA who were admitted to our hospital from February 2014 to February 2016 were retrospectively analyzed. They were randomly divided into control group( n = 30) and observation group( n = 30). The patients in the control group were treated with leflunomide,whereas those in the observation group were treated with methotrexate. The clinical efficacy and adverse reactions of the two groups were observed. The laboratory test indicators of the two groups before and after treatment,IL-1β and TNF-α in the culture supernatant of the synovial cell,levels of MMP-3 and DAS28 score were observed. Results After treatment,the total effective rate of the observation group and the control group was 90. 00% and 64. 52% respectively,and the difference between the groups was significant( P < 0. 05). Before treatment,there was no significant difference in the number of joint swelling,joint tenderness and ESR and CRP levels between the two groups( P > 0. 05). After treatment,the number of joint swelling and joint tenderness of the observation group were significantly lower than those of the control group( P < 0. 05); and the ESR and CRP indexes of the observation group were significantly lower than those of the control group( P < 0. 05). Before treatment,there was no significant difference in the levels of IL-1β,TNF-α and MMP-3 in the supernatant of cell culture medium between the two groups( P > 0. 05). After treatment,the levels of above indicators in the supernatant of the cell culture medium of the observation group were significantly lower than those of the control group( P < 0. 05). No significant difference was found in the DAS28 scores between the two groups before treatment( P > 0. 05). The DAS28 scores of the two groups were significantly lower after treatment than those before treatment( P < 0. 05),which were significantly lower in the observation group than in the control group( P < 0. 05). No significant difference was observed in the incidence of adverse reactions between the two groups( P > 0. 05). Conclusion Methotrexate has remarkable curative effects on,which can reduce the number of joint swelling and joint tenderness and ESR,CRP levels,moreover,which can improve the levels of IL-1β,TNF-α and MMP-3 in synovial cells of patients so as to inhibit bone destruction and improving DAS28 score,with good safety.
Objective To investigate the effects of methotrexate on inhibition of bone destruction,serum IL-1β and TNF-α in patients with rheumatoid arthritis( RA). Methods Clinical data of sixty patients with RA who were admitted to our hospital from February 2014 to February 2016 were retrospectively analyzed. They were randomly divided into control group( n = 30) and observation group( n = 30). The patients in the control group were treated with leflunomide,whereas those in the observation group were treated with methotrexate. The clinical efficacy and adverse reactions of the two groups were observed. The laboratory test indicators of the two groups before and after treatment,IL-1β and TNF-α in the culture supernatant of the synovial cell,levels of MMP-3 and DAS28 score were observed. Results After treatment,the total effective rate of the observation group and the control group was 90. 00% and 64. 52% respectively,and the difference between the groups was significant( P < 0. 05). Before treatment,there was no significant difference in the number of joint swelling,joint tenderness and ESR and CRP levels between the two groups( P > 0. 05). After treatment,the number of joint swelling and joint tenderness of the observation group were significantly lower than those of the control group( P < 0. 05); and the ESR and CRP indexes of the observation group were significantly lower than those of the control group( P < 0. 05). Before treatment,there was no significant difference in the levels of IL-1β,TNF-α and MMP-3 in the supernatant of cell culture medium between the two groups( P > 0. 05). After treatment,the levels of above indicators in the supernatant of the cell culture medium of the observation group were significantly lower than those of the control group( P < 0. 05). No significant difference was found in the DAS28 scores between the two groups before treatment( P > 0. 05). The DAS28 scores of the two groups were significantly lower after treatment than those before treatment( P < 0. 05),which were significantly lower in the observation group than in the control group( P < 0. 05). No significant difference was observed in the incidence of adverse reactions between the two groups( P > 0. 05). Conclusion Methotrexate has remarkable curative effects on,which can reduce the number of joint swelling and joint tenderness and ESR,CRP levels,moreover,which can improve the levels of IL-1β,TNF-α and MMP-3 in synovial cells of patients so as to inhibit bone destruction and improving DAS28 score,with good safety.
引文
1中华医学会风湿病学分会.类风湿关节炎诊断及治疗指南.中华风湿病学杂志,2010,14:265-270.
2 卓和伟,章磊,卢浩,等.黄芪对类风湿关节炎患者血清游离氨基酸与趋化因子的影响.中国生化药物杂志,2017,37:107-109.
3 中华医学会风湿病学分会.类风湿关节炎诊断及治疗指南.中华风湿病学杂志,2010,14:265-270.
4 周平.甲氨蝶呤联合来氟米特治疗类风湿关节炎患者临床疗效及安全性.中国老年学杂志,2014,:5717-5718.
5 吴会霞,任洁,朱丽花,等.托珠单抗与依那西普治疗类风湿关节炎疗效观察.暨南大学学报(自然科学与医学版),2016,37:358-362.
6 Derambure C,Dzangue-Tchoupou G,Berard C,et al. Pre-silencing of genes involved in the electron transport chain(ETC)pathway is associated with responsiveness to abatacept in rheumatoid arthritis.Arthritis Res Ther,2017,19:109.
7 毕丹艳,李芹,张虹,等.雷公藤多苷联合甲氨蝶呤治疗类风湿关节炎的临床疗效研究.中国临床药理学杂志,2016,32:880-882.
8 Thaniyan A,Ayman FFA,Mirghani HO,et al. Histopathological Features of Methotrexate Induced Pulmonary Lesions in Rheumatoid Arthritis Patients:A Systematic Review of Case Reports. Open Access Maced J Med Sci,2017,5:266-270.
9 黄玲玲,闫国跃,邓秋兰,等.瑶医药浴对改善类风湿关节炎患者临床症状的效果评价.护士进修杂志,2016,31:972-974.
10 Ikeda K,Watanabe K,Hirai T,et al. Mizoribine synchronized methotrexate therapy should be considered when treating rheumatoid arthritis patients with an inadequate response to various combination therapies. Intern Med,2017,56:1147-1152.
11 李培培,邰宇,黄传兵,等.美洛昔康片联合甲氨蝶呤片治疗类风湿关节炎的临床研究.中国临床药理学杂志,2016,32:2023-2026.
12 俞红五,朱艳,潘喻珍,等.艾灸辅助治疗类风湿关节炎患者临床疗效观察及机制探讨.中国针灸,2016,36:17-20.
13 Glaser C,Rieg S,Wiech T,et al. Whipple’s disease mimicking rheumatoid arthritis can cause misdiagnosis and treatment failure.Orphanet J Rare Dis,2017,25,12:99.
14 兰瑛,胡蝶,宋海宁,等.甲氨蝶呤治疗类风湿关节炎有效性与安全性的系统评价.中国药房,2016,27:2928-2932,2933.
15 韩丹.双醋瑞因联合甲氨蝶呤和来氟米特治疗老年人类风湿关节炎的疗效分析.中华老年医学杂志,2014,33:775-778.
2 卓和伟,章磊,卢浩,等.黄芪对类风湿关节炎患者血清游离氨基酸与趋化因子的影响.中国生化药物杂志,2017,37:107-109.
3 中华医学会风湿病学分会.类风湿关节炎诊断及治疗指南.中华风湿病学杂志,2010,14:265-270.
4 周平.甲氨蝶呤联合来氟米特治疗类风湿关节炎患者临床疗效及安全性.中国老年学杂志,2014,:5717-5718.
5 吴会霞,任洁,朱丽花,等.托珠单抗与依那西普治疗类风湿关节炎疗效观察.暨南大学学报(自然科学与医学版),2016,37:358-362.
6 Derambure C,Dzangue-Tchoupou G,Berard C,et al. Pre-silencing of genes involved in the electron transport chain(ETC)pathway is associated with responsiveness to abatacept in rheumatoid arthritis.Arthritis Res Ther,2017,19:109.
7 毕丹艳,李芹,张虹,等.雷公藤多苷联合甲氨蝶呤治疗类风湿关节炎的临床疗效研究.中国临床药理学杂志,2016,32:880-882.
8 Thaniyan A,Ayman FFA,Mirghani HO,et al. Histopathological Features of Methotrexate Induced Pulmonary Lesions in Rheumatoid Arthritis Patients:A Systematic Review of Case Reports. Open Access Maced J Med Sci,2017,5:266-270.
9 黄玲玲,闫国跃,邓秋兰,等.瑶医药浴对改善类风湿关节炎患者临床症状的效果评价.护士进修杂志,2016,31:972-974.
10 Ikeda K,Watanabe K,Hirai T,et al. Mizoribine synchronized methotrexate therapy should be considered when treating rheumatoid arthritis patients with an inadequate response to various combination therapies. Intern Med,2017,56:1147-1152.
11 李培培,邰宇,黄传兵,等.美洛昔康片联合甲氨蝶呤片治疗类风湿关节炎的临床研究.中国临床药理学杂志,2016,32:2023-2026.
12 俞红五,朱艳,潘喻珍,等.艾灸辅助治疗类风湿关节炎患者临床疗效观察及机制探讨.中国针灸,2016,36:17-20.
13 Glaser C,Rieg S,Wiech T,et al. Whipple’s disease mimicking rheumatoid arthritis can cause misdiagnosis and treatment failure.Orphanet J Rare Dis,2017,25,12:99.
14 兰瑛,胡蝶,宋海宁,等.甲氨蝶呤治疗类风湿关节炎有效性与安全性的系统评价.中国药房,2016,27:2928-2932,2933.
15 韩丹.双醋瑞因联合甲氨蝶呤和来氟米特治疗老年人类风湿关节炎的疗效分析.中华老年医学杂志,2014,33:775-778.