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痹清饮治疗类风湿关节炎的疗效观察及对滑膜细胞的干预作用
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摘要
本研究运用祖国医学和中西医结合理论,从理论、临床及实验三方面对活动期类风湿关节炎(rheumatoid arthritis,RA)的病变机理进行了深入的系统探讨。学生在张鸣鹤教授及导师周翠英教授的悉心指导下,提出“热毒成因论”和“热毒致痹论”的理论,认为湿热瘀毒痹阻经络、流注肢节是活动期RA的主要病机,临床以清热解毒为主要治法,兼以利湿通络、活血化瘀。拟定痹清饮合甲氨蝶呤为试验组,以帕夫林(白芍总苷)合甲氨蝶呤为对照组,采用美国风湿病学院所制定的ACR20、ACR50、ACR70来评价疗效,共观察60例患者(两组均为30例)。结果显示:试验组ACR20、ACR50、ACR70有效率均高于对照组,但两组间比较差异无统计学意义(P>0.05);中医证候疗效分析,两组总有效率无显著性差异(P>0.05),控显率比较有显著性差异(P<0.05),证候疗效的控显率试验组优于对照组;两组在改善临床症状、体征、实验室指标等方面均有效,试验组优于对照组(P<0.01或P<0.05);试验组和对照组均具有良好的安全性,两组间无统计学意义(P>0.05);而试验组具有良好的耐受性,与对照组相比有统计学意义(P<0.05)。实验研究旨在观察RA成纤维样滑膜(fibroblast-like synoviocytes,FLS)细胞的生长特点,应用MTT法、流式细胞仪和RT-PCR等多种方法,检测不同浓度的痹清饮对RA-FLS增殖与分化的影响,并与白芍总苷对照。实验结果表明:痹清饮和白芍总苷均能抑制FLS增殖;痹清饮可抑制FLS有丝分裂,缩短S期,延长G1期;痹清饮提高FLS bax mRNA表达,降低FLS bcl-2 mRNA表达,提示痹清饮对细胞增殖的抑制直接发生在转录水平,与白芍总苷的作用相似。结论:“热毒成因论”和“热毒致痹论”为活动期RA发病及发展转归的主要环节,痹清饮治疗活动期RA的疗效机理在于抗感染,抗炎、镇痛、抑制免疫炎症反应,调节免疫力功能和改善凝血纤溶机制;其作用机理在于痹清饮能抑制RA-FLS增殖与分化。
This study makes further exploration of the pathology mechanism of active rheumatoid arthritis(RA) in theory, clinical and experimental tripartite face with theories of TCM and Western Medicine Combined. The theories of“heat-toxicant etiology”and“heat-toxicant causing rheumatism doctrine”are advanced under the guidance of professor Zhang Minghe and my tutor professor Zhou Cuiying.We think that main pathology mechanism of RA in periods of activity is damp-heat and stasis -toxicant obstructing channels and flowing to limbs’joints. The key treatment methods are clearing away heat and toxic materials, clearing away dampness to remove obstruction in the channels and promoting blood circulation to remove blood stasis. 60 patients were divided into two groups(test group 30 patients and control group 30 patients).The patients in test group were treated by Biqing-drink decoction and Methotrexate, those in control group were treated by Pafulin(Radix Paeoniae Alba glycosides ) . The standards of curative effect are ACR20,ACR50 and ACR70 made by rheumatism institute of U.S.A. Results: the test group ACR20, ACR50, ACR70 efficiency were higher than the controls, but the difference between the two groups was not significant (P> 0.05); Syndrome effect of Chinese medicine, the total efficiency of the two groups no significant difference ( P> 0.05), the rate charged was more significant difference (P <0.05), Syndrome effect in controlling the rate of the test group than the control group were to improve the clinical symptoms and signs, laboratory and other aspects of effective indicators, The test group than the control group (P <0.01, or P <0.05); test group and control group has a good safety, between the two groups was not significant (P> 0.05); test group and has a good tolerance , Compared with the control group had a significant (P <0.05). Experimental study aimed to investigate RA fibroblast-like synoviocytes (fibroblast-like synoviocytes, FLS) cell growth characteristics, the application of MTT, flow cytometry and RT-PCR, and other methods to detect different concentrations of the Biqing-drink on RA FLS -proliferation and differentiation, and control of TGP.The results showed that: Both Biqing-drink and TGP can inhibit the proliferation of FLS; Biqing-drink can inhibit the FLS mitosis, shortening S phase, to extend G1 phase; Biqing-drink increase FLS bax mRNA expression, lower FLS bcl-2 mRNA expression , suggesting that the Biqing-drink directly inhibit cell proliferation in the transcription level, and the role of TGP similar. Conclusion: "Toxic Heat causes theory" and "Toxic Heat to Bi" for the incidence of active RA and the outcome of major aspects of development, the efficacy of Biqing-drink treats active RA may in the anti-infective, anti-inflammatory, analgesic, inhibit immune inflammatory response, regulate immune function and improve the mechanism of coagulation and fibrinolysis;Its mechanism is that Biqing-drink can inhibit the proliferation and differentiation of RA-FLS.
引文
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