苦参碱对类风湿关节炎外周血淋巴细胞生长、细胞周期及IFN-γ、IL-4水平影响的研究
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摘要
目的
在体外实验中,通过比较中药苦参碱(Mat Matrine)与甲氨蝶呤(MTX Methotrexate)对类风湿关节炎患者外周血淋巴细胞(PBL)生长、细胞周期及IFN-γ与IL-4分泌水平的影响,探讨Mat对类风湿关节炎PBL的作用机制。
方法
1.分离纯化外周血淋巴细胞,进行体外培养,选取MTX和Mat两种药物,各设6个浓度,其中O浓度为对照组。
2.应用MTT比色法测定24小时和48小时的MTX处理组、Mat处理组的吸光度值(A),计算细胞抑制率。
3.应用碘化丙啶(PI)染色流式细胞术(FCM)检测48小时MTX处理组、Mat处理组的细胞周期;
4.应用酶联免疫吸附试验(ELISA法)检测MTX处理组、Mat处理组的IFN-γ与IL-4的分泌水平。
结果
1.MTX、Mat均可抑制体外培养的PBL生长,随着药物浓度的增大,吸光度值(A)下降,细胞抑制率(IR%)增加,呈剂量依赖性。48h作用点细胞抑制率(IR%)明显大于24h作用点(P＜0.001)。两药物比较无明显差别(P＞0.05)。
2.MTX、Mat均可使细胞周期构成发生明显变化,与对照组相比存在显著差异(P＜0.001),G_0/G_1期细胞比例增高,S期和G_2/M期细胞比例降低。随着药物浓度增加,细胞增殖指数逐渐降低,呈剂量依赖性。两药物比较无明显差别(P＞0.05)。
3.MTX、Mat均可降低促炎因子IFN-γ分泌水平,与对照组相比存在显著差别(P＜0.001),但Mat组IFN-γ分泌水平降低幅度小于MTX组(P＜0.001)。MTX、Mat组IL-4分泌水平与对照组无明显差别(P＞0.05)。
结论
1.Mat抑制体外培养的RA患者PBL生长的作用与MTX相当。
2.Mat对PBL细胞周期的阻滞作用与MTX相当。
3.与MTX相比,Mat可下调IFN-γ分泌水平,Mat作用弱于MTX。MTX、Mat对IL-4分泌水平无明显影响。
4.Mat、MTX作用机制有相似性,推测Mat可能具有治疗RA的潜在价值。
Objective
To investigate the effects of Matrine(Mat)on cell proliferation,cell cycling and cytokines of the peripheral blood lymphocyte in patients with rheumatoid arthritis.Furthermore,through contrast with methotrexate(MTX),try to find out the mechanism of treatment for rheumatoid arthritis(RA).
Method
1.Separate and purify lymphocyte cells.Culture lymphocyte cells outside of body.Choose Methotrexate and Matrine.
2.The level of cell proliferation was measured by the MTT method.
3.Cell cycle was measured by flow cytometry with PI Staining(FCM)method.
4.The level of IFN-γand IL-4 was measured with ELISA.
Result
1.Both MTX and Mat can inhibit the proliferation of PBL in patients with RA and the effect is dose-dependent.It makes IR%increasing.(P＜0.05).IR%of 48h is more than IR%of 24h(P＜0.001).The two medicine have no obvious difference(P＞0.05).
2.Both MTX and Mat can change the cell cycle and act in G_1/S point.They both make the number of cells in G_0/G_1 phase increasing and cells in S and G_2/M phase decreasing(P＜0.05). The two medicine have no obvious difference(P＞0.05).
3.Level of IFN-γof Mat-treated and MTX-treated groups dropped significantly compared with control group(P＜0.001).But the level of IFN-γof Mat-treated groups is more than MTX -treated groups.All of the groups had no effect in the production of IL-4 in these doses (P＞0.05).
Conclusion
1.Mat inhibites the proliferation of PBL in patients with RA.The effect is correspondent to MTX.
2.Mat inhibites proliferation-dependent processes of PBL in patients with RA.The effect is correspondent to MTX.
3.The effect on IFN-γof Mat is weaker than MTX.
4.The mechanism of Mat is similar to MTX.Mat maybe have the potential value in the treatment of RA.
在体外实验中,通过比较中药苦参碱(Mat Matrine)与甲氨蝶呤(MTX Methotrexate)对类风湿关节炎患者外周血淋巴细胞(PBL)生长、细胞周期及IFN-γ与IL-4分泌水平的影响,探讨Mat对类风湿关节炎PBL的作用机制。
方法
1.分离纯化外周血淋巴细胞,进行体外培养,选取MTX和Mat两种药物,各设6个浓度,其中O浓度为对照组。
2.应用MTT比色法测定24小时和48小时的MTX处理组、Mat处理组的吸光度值(A),计算细胞抑制率。
3.应用碘化丙啶(PI)染色流式细胞术(FCM)检测48小时MTX处理组、Mat处理组的细胞周期;
4.应用酶联免疫吸附试验(ELISA法)检测MTX处理组、Mat处理组的IFN-γ与IL-4的分泌水平。
结果
1.MTX、Mat均可抑制体外培养的PBL生长,随着药物浓度的增大,吸光度值(A)下降,细胞抑制率(IR%)增加,呈剂量依赖性。48h作用点细胞抑制率(IR%)明显大于24h作用点(P＜0.001)。两药物比较无明显差别(P＞0.05)。
2.MTX、Mat均可使细胞周期构成发生明显变化,与对照组相比存在显著差异(P＜0.001),G_0/G_1期细胞比例增高,S期和G_2/M期细胞比例降低。随着药物浓度增加,细胞增殖指数逐渐降低,呈剂量依赖性。两药物比较无明显差别(P＞0.05)。
3.MTX、Mat均可降低促炎因子IFN-γ分泌水平,与对照组相比存在显著差别(P＜0.001),但Mat组IFN-γ分泌水平降低幅度小于MTX组(P＜0.001)。MTX、Mat组IL-4分泌水平与对照组无明显差别(P＞0.05)。
结论
1.Mat抑制体外培养的RA患者PBL生长的作用与MTX相当。
2.Mat对PBL细胞周期的阻滞作用与MTX相当。
3.与MTX相比,Mat可下调IFN-γ分泌水平,Mat作用弱于MTX。MTX、Mat对IL-4分泌水平无明显影响。
4.Mat、MTX作用机制有相似性,推测Mat可能具有治疗RA的潜在价值。
Objective
To investigate the effects of Matrine(Mat)on cell proliferation,cell cycling and cytokines of the peripheral blood lymphocyte in patients with rheumatoid arthritis.Furthermore,through contrast with methotrexate(MTX),try to find out the mechanism of treatment for rheumatoid arthritis(RA).
Method
1.Separate and purify lymphocyte cells.Culture lymphocyte cells outside of body.Choose Methotrexate and Matrine.
2.The level of cell proliferation was measured by the MTT method.
3.Cell cycle was measured by flow cytometry with PI Staining(FCM)method.
4.The level of IFN-γand IL-4 was measured with ELISA.
Result
1.Both MTX and Mat can inhibit the proliferation of PBL in patients with RA and the effect is dose-dependent.It makes IR%increasing.(P＜0.05).IR%of 48h is more than IR%of 24h(P＜0.001).The two medicine have no obvious difference(P＞0.05).
2.Both MTX and Mat can change the cell cycle and act in G_1/S point.They both make the number of cells in G_0/G_1 phase increasing and cells in S and G_2/M phase decreasing(P＜0.05). The two medicine have no obvious difference(P＞0.05).
3.Level of IFN-γof Mat-treated and MTX-treated groups dropped significantly compared with control group(P＜0.001).But the level of IFN-γof Mat-treated groups is more than MTX -treated groups.All of the groups had no effect in the production of IL-4 in these doses (P＞0.05).
Conclusion
1.Mat inhibites the proliferation of PBL in patients with RA.The effect is correspondent to MTX.
2.Mat inhibites proliferation-dependent processes of PBL in patients with RA.The effect is correspondent to MTX.
3.The effect on IFN-γof Mat is weaker than MTX.
4.The mechanism of Mat is similar to MTX.Mat maybe have the potential value in the treatment of RA.
引文
[1]时步卿.类风湿关节炎患者血清TNF-α和外周血B淋巴及T细胞亚群的探讨.放射免疫学杂志,2006,197:199.
[2]冷建杭,胡晋勇,卓广超等.类风湿关节炎血B淋巴细胞其刺激分子的表达及其意义.中华内科杂志,2004,3(7):549-521.
[3]Zhixin Z,Bridges S L.Pathogenesis of rheumatoid arthritis:role of B lymphocytes.Rheumatic Disease Clinics of North America,2001,27(2):335-353.
[4]El Ewau TD,De KeyserG,De W ever N,et al.A comparative phenotypical analysis of rheumatoid nodules and rheumatoid synovium with special reference to adhesion molecules and activation markers[J].Ann Rheum D is 1998,57(8):480.
[5]Yudoh K,Matsuno H.[J].Arthritis Rheum,2000,43(3):617-627.
[6]张浩,董书魁,李雪丽等,类风湿关节炎患者外周血细胞IFN-γ和IL-4的三色流式分析.免疫学杂志,2004,20(2):138-143.
[7]张乃峥.风湿性疾病及细胞因子.临床风湿病学,1999,73-83.
[8]Simon A,Seipel T,Sieper J.Divergent T cell cytokine patterns in inflammatory arthritis[J].Proc Natl Acad Sci USA,1994,91:292.
[9]Hong KH,Cho ML,Min SY,et al.Effect of interleukin-4 on vascular endothelial growth factor production in rheumatoid synovial fibroblasts.Clin Exp Immunol.2007Mar;147(3):573-9.
[10]冯骥良,黄高舁,张永清等.苦参碱抑制JM细胞株增殖和诱导凋亡的研究[J].中国中药杂志,2003,28(5):437-442.
[11]王俊学,王国俊.苦参碱及氧化苦参碱的药理作用及临床应用[J].Chinese Hepatology,2000,5(2):116-117.
[12]Genestier L,Paillot R,Foumel S,et al.Immunosuppressive properties of methotrexate:apoptosis and clonal deletion of activated peripheral T cells.J Clin Invest,1998,120(2):322-328.
[13]de Lathouder S,Gerards AH,de Groot ER,et al.Mycophenolic acid and methotrexate inhibit lymphocyte cytokine production via different mechanisms.Eur Cytokine Netw,2002,12(13):317-323.
[14]Hornrng N,Stengaard PK,Ehrnrooth E,et al.The effects of lowdose methotrexate on thymidylate synthesis activity in human peripheral blood mononuclear cells and serum from patients with rheumatoid arthritis in different American college of rheumatology response groups to methotrexate.J Rheumatol,2003,30(1):28-35.
[15]Hornung N,Stengaard pk Ehrnrooth E,et al.The effects of lowdose methotrexate on thmidylate synthesis activety in humanperipheral blood mononuclear cell.Clin xp Rheumatol,2000,18(6):691-698.
[16]金艳书,吴学敏,娄金丽.苦参碱对人肝癌细胞增殖、细胞周期及细胞凋亡的影响.中国临床康复,2006,10(3):107-109.
[17]付燕燕,陈彦,吴键,等.苦参碱诱导HepG2细胞凋亡与cyclin D1和P27~(kipl)关系的实验.徐州医学院学报,2006,26(4):305-307.
[18]Sgambato A,Camerini A,Pani G,et al.Increased expression of cyclin E is associated with an increased resistance to doxorubicin in rat fibroblasts.Br J Cancer,2003,88:1956-1962.
[19]Fairbands L D,Ckemarm K R,Qin Y et al.Methotrexate nhibits the fist committd tep f purine biosymhesis in mioger stimulated human T-lymphocytes:a metaboh basis for efficacy in rheumatoid arthtitis?Biochm J,1999,342:143.
[20]刘巧红,沈凌汛,滕云等,甲氨蝶呤对类风湿关节炎滑膜细胞增生及细胞周期的影响,中华风湿病学杂志,2004,8(4):223-226
[21]周惠琼,吴东海.甲氨蝶呤治疗类风湿关节炎作用机制的研究进展.中国药物与临床,2004,4(7):497-499.
[22]Hornung N,Stengaard PK,Ehrnrooth E,et al.The effects of low-dose methotrexate on thymidylate synthesis activity in human peripheral blood mononuclear cells.Clin Exp Rheumatol,2000.,18(6):691-698.
[1]马伟光,张滔,张超,等.有毒药物雷公藤的研究及展望.中华中医药杂志,2006,21(2):117-120.
[2]王振刚.雷公藤多甙对健康人周围血单个核细胞IL-6和IL-8产生的影响.中国中西医结合杂志,1997,17(6):348-350.
[3]涂胜豪,胡永红,曾克勤,等.雷公藤内酯醇对胶原诱导的大鼠关节炎关节腔和外周血清中细胞因子的影响.安徽中医学院学报,2006,25(1):27-29.
[4]鲍一笑,张璐定,李莉,等.雷公藤红素对HMC-1细胞凋亡相关基因表达的影响.第二军医大学学报,2001,(9):833-835.
[5]王国春,吴东海.雷公藤对类风湿关节炎患者淋巴细胞亚群的影响.中华内科杂志,1994,(1):41-42.
[6]要庆平,张乃峥.雷公藤单体T4对类风湿关节炎患者及正常人外周血单个核细胞增殖的影响.中国医学科学院学报,1994,(5):352-354.
[7]郭垣,于孟学,姜玉娟,等.雷公藤单体T_4对IL-1刺激引起的类风湿患者关节滑膜成纤维细胞增殖和产生IL-6的影响.中国医学科学院学报,2000,22(2):190-192.
[8]要庆平,张乃峥.雷公藤单一有效成分T4对类风湿关节炎患者滑膜细胞产生前列腺素E2的影响.药学学报,1994,29(10):790-792.
[9]胡大伟,刘沛霖.雷公藤与强的松药理作用的互补性.中国中西医结合杂志,1997,17(2):94-96.
[10]吴柏林.雷公藤治疗类风湿关节炎的机理探要.Journal of Practical Traditional Chinese Internal Medicine,2003,3(17):150
[11]黄煌.雷公藤中毒31例临床分析.中华内科杂志,1982,(6):363.
[12]莫华敦.雷公藤引起尿崩症2例.中华肾脏病杂志,1989,(2):75.
[13]孔庆峰,李军.青藤碱研究新进展.中国中药杂志,2005,30(20):1573-1576.
[14]He X,Wang J,Guo Z,et al.Requirement fou ERK activation in sinomenine-induced apoptosis of macrophages.Immunol Lett.2005,98-91-96.
[15]Wang Y,Fang Y,Huang W,et al.Effect of sinomenine on cytokine expression of macrophages and synoviocytes in adjuvant arthritis rats.J Ethnopharmacol.2005,98(1-2):37-43
[16]李晓娟,王培训,刘良,等.青藤碱对T淋巴细胞活化及TH1类细胞内细胞因子表达的影响.中国免疫学杂志,2004,20:249-252.
[17]胜豪,胡永红,陆付耳.青藤碱对人淋巴细胞产生IL-2、IL-2R和IL-6的影响.中国实验临床免疫学杂志,1998,10(5):268.
[18]王文君,王培训,李晓娟.青藤碱抗炎机理——青藤碱对人外周血单个核细胞环氧化 酶活性及其基因表达的影响.中国中药杂志,2003,28(4):352-354.
[19]刘继红,李卫东,滕慧玲,林志彬.青藤碱治疗类风湿关节炎免疫作用和机制.药学学报,2005,40(2):127-131.
[20]黄清香,陈纪藩,陈光星,等.青藤碱对胶原诱导性关节炎大鼠滑膜细胞凋亡的影响.中国临床康复,2002,6(17):2541.
[21]刘晓玲,陈光星,李晓娟,等.青藤碱对Ⅱ型胶原诱导关节炎大鼠滑膜炎症的抑制作用及其机理讨论.广州中医药大学学报,2002,19:214-217.
[22]马云淑.青风藤碱的镇痛镇静作用.云南中医学院学报 1992,(4):9.
[23]季宇彬.中药有效成分药理与应用.哈尔滨:黑龙江科学技术出版社,1995,1:17.
[24]周强,栗占国.白芍总甙的药理作用及其在自身免疫性疾病中的应用.中国新药与临床杂志,2003,22(11):687-690.
[25]张鸿炼,吴文蔚.白芍总甙的药理作用与临床应用.中国医院药学杂志,1995,15(8):371-372.
[26]高本波.丹皮总甙和白芍总甙对自由基清除作用的影响.潍坊医学院学报,1996,18(1):43.
[27]王斌,姚余有,周爱武,等.白芍总甙对佐剂性关节炎大鼠损伤的保护作用.中国药理学与毒理学杂志,1996,10(3):211.
[28]沈玉先,魏伟,徐叔云,等.白芍总甙的药理作用及机制[A].吴曙光.抗炎免疫药理学进展[M].上海:第二军医大学出版社,1997.162-167.
[29]王志坚,陈敏珠,孙桂华,等.白芍总甙治疗类风湿关节炎的临床药理研究.中国药理学通报,1994,10(2):117-121.
[30]张凤玲,唐永,张景梅,等.苦参碱、氧化苦参碱的药理作用及其制剂的研究进展.河南中医学院学报,2004,19(112):84-86.
[31]闵伟琪,魏琴,李洪毓,等.白芍总苷治疗类风湿关节炎的多中心临床研究.中华风湿病学杂志,2005,9(8):487-491.
[32]戴岳,杭秉茜,黄朝林.山茱萸对炎症反应的抑制作用.中国中药杂志,1992,17(5):31-32.
[33]郭丽丽,周勇,王旭丹,等.山茱萸总苷对佐剂性关节炎大鼠原代滑膜细胞培养上清趋化能力的影响.北京中医药大学学报,2002,25:30-32.
[34]郭丽丽,周勇,王旭丹,等.山茱萸总苷抗类风湿关节炎免疫作用机理的初步研究.中国免疫学杂志,2002,18:197-199.
[35]郭丽丽,周勇,王旭丹,等.山茱萸分离提取物对脾淋巴细胞增殖的影响.北京中医药大学学报,2001,24(3):38-40.
[36]李雅江,李慧玲,邬剑.山茱萸对大鼠佐剂性关节炎的免疫治疗作用.中国老年学杂志,2004,24:265-266.
[37]周平,高玉祥.青蒿琥酯对小鼠免疫功能的影响.蚌埠医学院学报,1996,21(1):55.
[38]李文桂,陈雅棠,刘成伟,等.双氢青蒿素对患卡氏肺孢子虫肺炎大鼠血清和肺泡巨噬细胞上清液IL-1水平的影响.地方病通报,2002,17(4):12-15.
[39]Tan Y.Experimental study on antiedotoxin dffect of extracts from Arte misia annua L.Zhongguo Zhong Yao Za Zhi,1999,24(3):166-167.
[40]丁小芬,胡红.青蒿治疗类风湿性关节炎的免疫药理作用.中国中医基础医学杂志,2006,12(1):75-76.
[41]黄黎.中药青蒿的解热抗炎作用研究.中国中药杂志,1993,18(1):44-48.
[42]Nagy L,Kao H Y,Chakravarti K,et al.Nuclear recptor repreression mediated by a complex containing SMRT,mS in3A,and histone deacetylase.Cell,1997,89:373.
[43]易剑峰,王珏,林色奇,等.青蒿素及其衍生物免疫调节研究概况.江西中医学院学报,2006,18(1):69-71.
[44]范志云,罗红,刘玉兰,等.川芎嗪的抗炎作用与组胺、5-羟色胺的关系.中药新药与临床药理,2004,15(2):93-95.
[45]王建杰,罗文哲,张涛,等.川芎嗪对老年类风湿关节炎外周血单个核细胞IL-2mRNA 表达及Ig合成的影响.中国中医基础医学杂志,2006,12(1):1395-1396.
[2]冷建杭,胡晋勇,卓广超等.类风湿关节炎血B淋巴细胞其刺激分子的表达及其意义.中华内科杂志,2004,3(7):549-521.
[3]Zhixin Z,Bridges S L.Pathogenesis of rheumatoid arthritis:role of B lymphocytes.Rheumatic Disease Clinics of North America,2001,27(2):335-353.
[4]El Ewau TD,De KeyserG,De W ever N,et al.A comparative phenotypical analysis of rheumatoid nodules and rheumatoid synovium with special reference to adhesion molecules and activation markers[J].Ann Rheum D is 1998,57(8):480.
[5]Yudoh K,Matsuno H.[J].Arthritis Rheum,2000,43(3):617-627.
[6]张浩,董书魁,李雪丽等,类风湿关节炎患者外周血细胞IFN-γ和IL-4的三色流式分析.免疫学杂志,2004,20(2):138-143.
[7]张乃峥.风湿性疾病及细胞因子.临床风湿病学,1999,73-83.
[8]Simon A,Seipel T,Sieper J.Divergent T cell cytokine patterns in inflammatory arthritis[J].Proc Natl Acad Sci USA,1994,91:292.
[9]Hong KH,Cho ML,Min SY,et al.Effect of interleukin-4 on vascular endothelial growth factor production in rheumatoid synovial fibroblasts.Clin Exp Immunol.2007Mar;147(3):573-9.
[10]冯骥良,黄高舁,张永清等.苦参碱抑制JM细胞株增殖和诱导凋亡的研究[J].中国中药杂志,2003,28(5):437-442.
[11]王俊学,王国俊.苦参碱及氧化苦参碱的药理作用及临床应用[J].Chinese Hepatology,2000,5(2):116-117.
[12]Genestier L,Paillot R,Foumel S,et al.Immunosuppressive properties of methotrexate:apoptosis and clonal deletion of activated peripheral T cells.J Clin Invest,1998,120(2):322-328.
[13]de Lathouder S,Gerards AH,de Groot ER,et al.Mycophenolic acid and methotrexate inhibit lymphocyte cytokine production via different mechanisms.Eur Cytokine Netw,2002,12(13):317-323.
[14]Hornrng N,Stengaard PK,Ehrnrooth E,et al.The effects of lowdose methotrexate on thymidylate synthesis activity in human peripheral blood mononuclear cells and serum from patients with rheumatoid arthritis in different American college of rheumatology response groups to methotrexate.J Rheumatol,2003,30(1):28-35.
[15]Hornung N,Stengaard pk Ehrnrooth E,et al.The effects of lowdose methotrexate on thmidylate synthesis activety in humanperipheral blood mononuclear cell.Clin xp Rheumatol,2000,18(6):691-698.
[16]金艳书,吴学敏,娄金丽.苦参碱对人肝癌细胞增殖、细胞周期及细胞凋亡的影响.中国临床康复,2006,10(3):107-109.
[17]付燕燕,陈彦,吴键,等.苦参碱诱导HepG2细胞凋亡与cyclin D1和P27~(kipl)关系的实验.徐州医学院学报,2006,26(4):305-307.
[18]Sgambato A,Camerini A,Pani G,et al.Increased expression of cyclin E is associated with an increased resistance to doxorubicin in rat fibroblasts.Br J Cancer,2003,88:1956-1962.
[19]Fairbands L D,Ckemarm K R,Qin Y et al.Methotrexate nhibits the fist committd tep f purine biosymhesis in mioger stimulated human T-lymphocytes:a metaboh basis for efficacy in rheumatoid arthtitis?Biochm J,1999,342:143.
[20]刘巧红,沈凌汛,滕云等,甲氨蝶呤对类风湿关节炎滑膜细胞增生及细胞周期的影响,中华风湿病学杂志,2004,8(4):223-226
[21]周惠琼,吴东海.甲氨蝶呤治疗类风湿关节炎作用机制的研究进展.中国药物与临床,2004,4(7):497-499.
[22]Hornung N,Stengaard PK,Ehrnrooth E,et al.The effects of low-dose methotrexate on thymidylate synthesis activity in human peripheral blood mononuclear cells.Clin Exp Rheumatol,2000.,18(6):691-698.
[1]马伟光,张滔,张超,等.有毒药物雷公藤的研究及展望.中华中医药杂志,2006,21(2):117-120.
[2]王振刚.雷公藤多甙对健康人周围血单个核细胞IL-6和IL-8产生的影响.中国中西医结合杂志,1997,17(6):348-350.
[3]涂胜豪,胡永红,曾克勤,等.雷公藤内酯醇对胶原诱导的大鼠关节炎关节腔和外周血清中细胞因子的影响.安徽中医学院学报,2006,25(1):27-29.
[4]鲍一笑,张璐定,李莉,等.雷公藤红素对HMC-1细胞凋亡相关基因表达的影响.第二军医大学学报,2001,(9):833-835.
[5]王国春,吴东海.雷公藤对类风湿关节炎患者淋巴细胞亚群的影响.中华内科杂志,1994,(1):41-42.
[6]要庆平,张乃峥.雷公藤单体T4对类风湿关节炎患者及正常人外周血单个核细胞增殖的影响.中国医学科学院学报,1994,(5):352-354.
[7]郭垣,于孟学,姜玉娟,等.雷公藤单体T_4对IL-1刺激引起的类风湿患者关节滑膜成纤维细胞增殖和产生IL-6的影响.中国医学科学院学报,2000,22(2):190-192.
[8]要庆平,张乃峥.雷公藤单一有效成分T4对类风湿关节炎患者滑膜细胞产生前列腺素E2的影响.药学学报,1994,29(10):790-792.
[9]胡大伟,刘沛霖.雷公藤与强的松药理作用的互补性.中国中西医结合杂志,1997,17(2):94-96.
[10]吴柏林.雷公藤治疗类风湿关节炎的机理探要.Journal of Practical Traditional Chinese Internal Medicine,2003,3(17):150
[11]黄煌.雷公藤中毒31例临床分析.中华内科杂志,1982,(6):363.
[12]莫华敦.雷公藤引起尿崩症2例.中华肾脏病杂志,1989,(2):75.
[13]孔庆峰,李军.青藤碱研究新进展.中国中药杂志,2005,30(20):1573-1576.
[14]He X,Wang J,Guo Z,et al.Requirement fou ERK activation in sinomenine-induced apoptosis of macrophages.Immunol Lett.2005,98-91-96.
[15]Wang Y,Fang Y,Huang W,et al.Effect of sinomenine on cytokine expression of macrophages and synoviocytes in adjuvant arthritis rats.J Ethnopharmacol.2005,98(1-2):37-43
[16]李晓娟,王培训,刘良,等.青藤碱对T淋巴细胞活化及TH1类细胞内细胞因子表达的影响.中国免疫学杂志,2004,20:249-252.
[17]胜豪,胡永红,陆付耳.青藤碱对人淋巴细胞产生IL-2、IL-2R和IL-6的影响.中国实验临床免疫学杂志,1998,10(5):268.
[18]王文君,王培训,李晓娟.青藤碱抗炎机理——青藤碱对人外周血单个核细胞环氧化 酶活性及其基因表达的影响.中国中药杂志,2003,28(4):352-354.
[19]刘继红,李卫东,滕慧玲,林志彬.青藤碱治疗类风湿关节炎免疫作用和机制.药学学报,2005,40(2):127-131.
[20]黄清香,陈纪藩,陈光星,等.青藤碱对胶原诱导性关节炎大鼠滑膜细胞凋亡的影响.中国临床康复,2002,6(17):2541.
[21]刘晓玲,陈光星,李晓娟,等.青藤碱对Ⅱ型胶原诱导关节炎大鼠滑膜炎症的抑制作用及其机理讨论.广州中医药大学学报,2002,19:214-217.
[22]马云淑.青风藤碱的镇痛镇静作用.云南中医学院学报 1992,(4):9.
[23]季宇彬.中药有效成分药理与应用.哈尔滨:黑龙江科学技术出版社,1995,1:17.
[24]周强,栗占国.白芍总甙的药理作用及其在自身免疫性疾病中的应用.中国新药与临床杂志,2003,22(11):687-690.
[25]张鸿炼,吴文蔚.白芍总甙的药理作用与临床应用.中国医院药学杂志,1995,15(8):371-372.
[26]高本波.丹皮总甙和白芍总甙对自由基清除作用的影响.潍坊医学院学报,1996,18(1):43.
[27]王斌,姚余有,周爱武,等.白芍总甙对佐剂性关节炎大鼠损伤的保护作用.中国药理学与毒理学杂志,1996,10(3):211.
[28]沈玉先,魏伟,徐叔云,等.白芍总甙的药理作用及机制[A].吴曙光.抗炎免疫药理学进展[M].上海:第二军医大学出版社,1997.162-167.
[29]王志坚,陈敏珠,孙桂华,等.白芍总甙治疗类风湿关节炎的临床药理研究.中国药理学通报,1994,10(2):117-121.
[30]张凤玲,唐永,张景梅,等.苦参碱、氧化苦参碱的药理作用及其制剂的研究进展.河南中医学院学报,2004,19(112):84-86.
[31]闵伟琪,魏琴,李洪毓,等.白芍总苷治疗类风湿关节炎的多中心临床研究.中华风湿病学杂志,2005,9(8):487-491.
[32]戴岳,杭秉茜,黄朝林.山茱萸对炎症反应的抑制作用.中国中药杂志,1992,17(5):31-32.
[33]郭丽丽,周勇,王旭丹,等.山茱萸总苷对佐剂性关节炎大鼠原代滑膜细胞培养上清趋化能力的影响.北京中医药大学学报,2002,25:30-32.
[34]郭丽丽,周勇,王旭丹,等.山茱萸总苷抗类风湿关节炎免疫作用机理的初步研究.中国免疫学杂志,2002,18:197-199.
[35]郭丽丽,周勇,王旭丹,等.山茱萸分离提取物对脾淋巴细胞增殖的影响.北京中医药大学学报,2001,24(3):38-40.
[36]李雅江,李慧玲,邬剑.山茱萸对大鼠佐剂性关节炎的免疫治疗作用.中国老年学杂志,2004,24:265-266.
[37]周平,高玉祥.青蒿琥酯对小鼠免疫功能的影响.蚌埠医学院学报,1996,21(1):55.
[38]李文桂,陈雅棠,刘成伟,等.双氢青蒿素对患卡氏肺孢子虫肺炎大鼠血清和肺泡巨噬细胞上清液IL-1水平的影响.地方病通报,2002,17(4):12-15.
[39]Tan Y.Experimental study on antiedotoxin dffect of extracts from Arte misia annua L.Zhongguo Zhong Yao Za Zhi,1999,24(3):166-167.
[40]丁小芬,胡红.青蒿治疗类风湿性关节炎的免疫药理作用.中国中医基础医学杂志,2006,12(1):75-76.
[41]黄黎.中药青蒿的解热抗炎作用研究.中国中药杂志,1993,18(1):44-48.
[42]Nagy L,Kao H Y,Chakravarti K,et al.Nuclear recptor repreression mediated by a complex containing SMRT,mS in3A,and histone deacetylase.Cell,1997,89:373.
[43]易剑峰,王珏,林色奇,等.青蒿素及其衍生物免疫调节研究概况.江西中医学院学报,2006,18(1):69-71.
[44]范志云,罗红,刘玉兰,等.川芎嗪的抗炎作用与组胺、5-羟色胺的关系.中药新药与临床药理,2004,15(2):93-95.
[45]王建杰,罗文哲,张涛,等.川芎嗪对老年类风湿关节炎外周血单个核细胞IL-2mRNA 表达及Ig合成的影响.中国中医基础医学杂志,2006,12(1):1395-1396.