用户名: 密码: 验证码:
制川乌与白芍组分配伍治疗类风湿性关节炎的作用机理研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的:从制川乌与白芍组分配伍层面上研究其抗炎、镇痛、解毒、以及治疗类风湿性关节炎的作用,确定其增效的最佳配伍组分和最佳配伍比例,探讨制川乌与白芍组分配伍治疗类风湿性关节炎的作用机理。
     方法:从制川乌与白芍配伍水煎液和组分配伍两个层面,采用热板致痛试验、乙酸扭体致痛试验、二甲苯耳廓肿胀试验、蛋清足肿胀试验、风寒湿证类风湿性关节炎模型,研究其抗炎、镇痛以及治疗类风湿性关节炎的作用,同时采用急性毒性实验研究其组分配伍的解毒作用,确定其配伍增效、解毒以及治疗类风湿性关节炎的最佳配伍组分和最佳配伍比例。通过观察风寒湿证类风湿性关节炎下丘脑EOP(L-ENK、β-END)、血浆SP、血清细胞因子(1L-1β、TNF-α、IL-6、IL-2、IL-10)、血清IgG、滑膜细胞的超微结构等指标,探讨制川乌与白芍配伍组分配伍治疗类风湿性关节炎的作用机理。
     结果:1、制川乌与白芍配伍水煎液有明显提高热板致痛小鼠痛阈值、冰乙酸致痛小鼠痛阈值和抑制小鼠二甲苯耳廓肿胀的作用;制川乌与白芍配伍水煎液有明显提高风寒湿证类风湿性关节炎大鼠左、右关节痛阈的作用,有抑制风寒湿证类风湿性关节炎大鼠左、右关节肿胀,原发性和继发性关节病理改变的作用;并且大部分配伍比例效果优于单煎液,其中,制川乌与白芍1:2配伍水煎液效果最为明显。2、制川乌与白芍组分配伍有明显提高冰乙酸致痛小鼠痛阈值和热板致痛小鼠痛阈值的作用,有明显抑制小鼠二甲苯耳廓肿胀和大鼠蛋清足肿胀的作用:各组分中,制川乌总碱与白芍总苷、白芍多糖配伍的镇痛和抗炎作用较为明显;各配伍比例中,1:2配伍效果最为明显。制川乌总碱与白芍总苷、白芍多糖配伍有明显提高风寒湿证类风湿性关节炎大鼠左、右关节痛阈值的作用,有明显抑制风寒湿证类风湿性关节炎大鼠左、右关节肿胀、胸腺萎缩、脾脏肿大、原发性和继发性关节病理改变的作用;并且1:2配伍效果优于单组分。3、制川乌总碱与白芍总苷、白芍多糖不同比例配伍后LD_(50)均较制川乌总碱的LD_(50)明显增大;白芍总苷、白芍多糖可以降低制川乌总碱毒性。4、制川乌总碱与白芍总苷、白芍多糖配伍可以提高大鼠下丘脑的L-ENK和β-END的含量,降低血浆SP含量,升高血清IL-1β、IL-6含量,降低血清IL-2、IL-10含量;并且1:2配伍效果优于单组分。
     结论:制川乌与白芍配伍水煎液有明显镇痛、抗炎和治疗风寒湿证类风湿性关节炎的作用;其中,制川乌与白芍1:2配伍水煎液效果最明显。制川乌与白芍组分配伍有明显镇痛、抗炎和治疗风寒湿证类风湿性关节炎的作用;其中,制川乌总碱与白芍总苷或白芍多糖1:2配伍效果最明显。制川乌总碱与白芍总苷或白芍多糖配伍后毒性降低。制川乌总碱与白芍总苷或白芍多糖配伍治疗风寒湿证类风湿性关节炎的作用机理可能是增加中枢EOP的含量,抑制P物质合成和释放入血浆,调节血清细胞因子的紊乱,抑制血清免疫球蛋白的合成和分泌,减轻滑膜细胞异常亢进的分泌功能。
Objective:To research the compatibility of composition about Radix Aconiti preparata and Raidix Paeoniae Alba on anti-inflammation effect,analgesia effect, deintoxication and curing rheumatoid arthritis.Find the best compatibility composition and proportion of synergistic effect.Explore the mechanism of action on compatibility composition curing rheumatoid arthritis.
     Methods:The pain test induced by hot-plate,the body-twisting test induced by acetic acid,the swelling test of the auricles induced by Xylene,the swelling degree test of feet induced by egg white and cold and dampness syndrome rheumatoid arthritis model of were used to research the compatibility effect of the water decoction and composition about Radix Aconiti preparata and Raidix Paeoniae Alba on anti-inflammation and analgesia and curing rheumatoid arthritis,and the acute toxicity test were used to research deintoxication.We found the best compatibility composition and proportion of synergistic effect,detoxication and curing rheumatoid arthritis.Finally,observed these indices such as endogenous opioid peptides(L-ENK,β-END) of hypothalamus,substance P,IgG of blood plasma,cell factors(IL-1β、TNF-a、IL-6、IL-2、IL-10) of blood plasma and the ultramicrostructure of synovial cell, we have explored the mechanism of action on compatibility composition curing rheumatoid arthritis.
     Results:1.The compatibility water decoction about Radix Aconiti preparata and Raidix Paeoniae Alba could elevate the pain threshold of mouse induced by hot-plate and acetic acid,and restrain the swelling of the mouse auricles induced by Xylene. The compatibility water decoction about Radix Aconiti preparata and Raidix Paeoniae Alba could elevate the pain threshold,and restrain the swelling and pathological changes of rats' left or right articulus of rheumatoid arthritis of cold and dampness syndrome.The effect of most of the compatibility water decoction was better than single water decoction.The best compatibility proportion was 1:2.2.The compatibility composition about Radix Aconiti preparata and Raidix Paeoniae Alba could elevate the pain threshold of mouse induced by hot-plate and acetic acid,and restrain the swelling of the mouse auricles induced by Xylene or the rats feet induced by egg white.The compatibility composition between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony had better analgesia effect and anti-inflammation effect.The best compatibility proportion was 1:2.The compatibility composition between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony could elevate the pain threshold,and restrain the swelling,pathological changes of rats' left or right articulus, Atrophy of thymus gland,tumidity of spleen of rheumatoid arthritis of cold and dampness syndrome.The effect of 1:2 was better than single composition.3.The LD_(50) of All compatibility proportion between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony became more than total base of Radix Aconiti preparata,therefore,total glucosides of paeony or polysaccharides of paeony could diminish the toxicity of total base of Radix Aconiti preparata.4.The compatibility composition between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony could elevate the contents of hypothalamic L-ENK andβ-END,degrade the contents of plasmatic SP,elevate the contents of serumal IL-1βand IL-6,degrade the contents of serumal IL-2 and IL-10.The effect of 1:2 was better than single composition.
     Conclusions:The compatibility water decoction about Radix Aconiti preparata and Raidix Paeoniae Alba had obviously the effect of analgesia,anti-inflammation,and curing rheumatoid arthritis.The best compatibility proportion was 1:2.The compatibility composition about Radix Aconiti preparata and Raidix Paeoniae Alba had obviously the effect of analgesia,anti-inflammation,and curing rheumatoid arthritis.The best compatibility compositions were between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony.The best compatibility proportion was 1:2.The toxicity of compatibility composition between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony decreased.The compatibility composition between total base of Radix Aconiti preparata with total glucosides of paeony or polysaccharides of paeony could cure rheumatoid arthritis.The mechanism of action might be that the contents of center EOP had increased,the synthesis and release of SP had been restrained,the disturbance of serumal cell factor had been adjusted,the synthesis and secretion of serum immune globulin had been restrained,and the anomal-excitatory secretory action of synovial cell had been relieved.
引文
[1]叶任高,陆再英.内科学[M].北京:人民卫生出版社,2002:897-903.
    [2]彭怀仁.中医方剂大辞典[M].北京:人民卫生出版社,1996.
    [3]李晋奇,王岚,彭成.川乌配伍白芍的现代临床应用与药理研究浅忻[J].中医药学刊,2003:21(12):2013-2014.
    [4]李晋奇,彭成.制川乌配伍白芍的增效作用及其作用机理[J].华西药学杂志,2007:22(2):144-148.
    [5]徐叔云,卞如濂,陈修.药理实验方法学[M].北京:人民卫生出版社.2002:920-921.
    [6]金祝秋,郑建生,彭芝配.等.大鼠风寒湿痹证模型的建立与前列腺素E_2的关系[J].湖南中医学院学报,1996:16(1):40-42.
    [7]国家药典委员会.中华人民共和国药典(2005版一部)[M].北京:化学工业出版社,2005:27,68-69.
    [8]莫选荣,罗心静.类风湿性关节炎发病机制的研究进展[J].医学临床研究,2007;24(2):336-340.
    [9]于孟学,王迎雪,施全胜.类风湿性关节炎发病机理[J].基础医学与临床,1998;18(4):1-7.12
    [10]Feldmann M,Andreakos E,Smith C,et al.Is NF-KappaB a useful therapeutic target in rheumatoid arthritis?[J].Ann Rheum Dis,2002;61(suppl2):ii13-ii18.
    [11]费克香,晏年春.类风湿性关节炎与T淋巴细胞研究进展[J].日本医学介绍,2000;21(9):427.
    [12]李霞,孙健,范成明.细胞因子与类风湿关节炎[J].大连大学学报,2000:21(4):102-105.
    [13]路秀英.免疫细胞、细胞因子及其抑制物在类风湿性关节炎发生发展中的作用[J].国外医学免疫学分册,1993;(4):183-187.
    [14]马继兴.马王堆古医书考释[M].长沙:湖南科学技术出版社,1992:200.
    [15]王洪图.黄帝内经研究大成(中册)[M]。北京:北京出版社,1997:1602-1618.
    [16]张新梅.类风湿性关节炎免疫治疗研究进展[J].医学综述,2004;10(2):115-117.
    [17]严桂民.类风湿关节炎的基因治疗[J].中国新医药,2003:2(8):47-48.
    [18]Keystone EC.The role of tumor necrosis factor antagonism in clinical practice[J].J Rheumatol Suppl,1999;57:22-28.
    [19]雷英.类风湿性关节炎物理治疗进展.中国运动医学杂志,1999:18(4):357-359.
    [20]鲍春德.类风湿性关节炎治疗的现状及展望[J].上海医学,2003:26(7):449-452.
    [21]周学平,吴勉华.中医药治疗类风湿性关节炎的新观点[J].中国临床康复,2002:6(5): 624-625.
    [22]刘莉,魏晓燕.治痹八法[J].中医药信息,2001:15(3):74
    [23]国家中医药管理局《中华本草》编委会.中华本草(第三册)[M].上海:上海科学技术出皈社,1999:101-106,515-521.
    [24]魏·吴普,等述;清·孙星衍,孙冯翼辑.神农本草经[M].北京:科学技术文献出版社,1996:61.
    [25]杨广民,张志国.川乌 草乌 附子[M].北京:中国中医药出版社,2001:2-3.
    [26]张元素著:任应秋点校;应荐整理.医学启源引《历代医学名著全书》(第八册)[M].海口:海南国际新闻出版中心,1996:7669.
    [27]杨俊,方红.芍药[M].北京:中国中医药出版社,2001:19.
    [28]秦林,彭欣.论寒热配伍在痹证治疗中的意义[J].中国中药杂志,1999,24(2):112-114.
    [29]张仲景著;文隶校注.金匮要略方论[M].北京:中国书店出版社,1993:30.
    [30]清·沈目南著;曹炳章原辑;杨金萍,谭红主校.沈注金匮要略引《中国医学大成》(第八册)[M].北京:中国中医药出版社,1997:733.
    [31]湖北中医学院.金匮要略释义(新1版)[M].上海:上海人民出版社,1973.
    [32]明代·朱棣辑.普济方(一八五卷)[M].《文渊阁四库全书》电子版.上海人民出版社、迪志文化出版有限公司,2005:1,55.
    [33]邓中甲.方剂学[M].北京:中国中医药出版社,2003:27-28.
    [34]何伟,王宁,秦林,等.川乌与白芍配伍前后乌头碱和芍药苷煎出量的测定[J].中国药学杂志,2002;37(9):680-683.
    [35]余成浩,彭成,余葱葱,等.制川乌配伍白芍不同配伍比例对酯型生物碱含量的影响[J].都中医药大学学报,2007;30(4):43-45.
    [36]张少华,彭欣,秦林,等.乌-芍及乌-防配伍前后对实验性疼痛的影响[J].中草药,1999;30(8):595-598.
    [37]秦林,彭欣,李晓丽,等.川乌配伍白芍对实验性疼痛的影响[J].中国中药杂志,1999;24(10):629-632.
    [38]秦林,彭欣,张勤生,等.剂量变化对川乌配伍白芍镇痛作用的影响[J].山东中医药大学学报,1999;23(4):225-227.
    [39]张惠云,秦林,薛玲,等.川乌与白芍配伍前后抗炎作用的比较研究[J].山东中医药大学学报,2000;24(4):29-7300.
    [40]张惠云,秦林,薛玲,等.川乌配伍白芍的抗炎作用特点研究[J].中国中药杂志,2002;27(6):449-452.
    [41]薛玲,张惠云,秦林,等.川乌与白芍配伍前后对大鼠佐剂性关节炎的影响[J].中国中药杂志,2000:25(3):175-176.
    [42]秦林,彭欣,张少华,等.川乌配伍白芍对炎症因子及自由基的影响[J].中国中药杂志, 2000:25(6):370-373.
    [43]秦林,张少华,李晓丽,等.川乌与白芍配伍的免疫调节作用初探[J].中国中药杂志,2002:27(7):541-544.
    [44]秦林,彭欣,李晓丽,等.白芍与川乌配伍前后急性毒性实验研究[J].山东中医药大学学报,2000;24(6):453-455.
    [45]王绪辉,郑效文,施杞.肢体痹证的造模方法[J].上海中医药杂志,1986;(3):3-5.
    [46]王绪辉,朱显华,周恩元,等.风湿寒性关节痛实验模型及病理学研究[J].中医杂志,1990;(7):50-52.
    [47]徐成林,钟尧舜,宋举武.痹证动物模型研究-风寒湿对家兔关节的影响[J].新疆中医药,1989;(4):12-13,11.
    [48]Pearson CM,Wood FD.Studies of polyarthritis and other lesions induced in rats by injection of mycobacterial adjuvant,Ⅰ.General clinical and pathologic characteristics and some modifying factors[j].Arthritis Rheum,1959;2:440-459.
    [49]Trentham DE,Townes AS,Kang AH.Autoimmunity to type Ⅱ collagen an experimental model of arthritis[J].J Exper Med,1977;146(3):857-868.
    [50]王安民,吕爱平,曾晓莲,等.大鼠实验性痹证模型的建立及其病理学研究[J].中华中医骨伤科杂志,1988:(2):8-11.
    [51]吕爱平,艾景录,冀向东,等.大鼠肌腱和肌肉在实验性痹证中的病理学改变[J].中国骨伤,1993:6(3):7-8.
    [52]艾景录,吕爱平,徐世杰,等.性腺动能异常型肾虚痹证发生机理的实验研究[J].中国中医基础医学杂志,1995;1(1):42-44.
    [53]徐世杰,吕爱平,张春英,等.切除卵巢所致肾虚对Ⅱ型胶原诱导的关节炎小鼠IL-2和IL-6含量的影响[J].中国中医基础医学杂志,1998;4(10):33-35.
    [54]徐世杰,吕爱平,王安民,等.切除卵巢所致肾虚对免疫性关节炎小鼠血清钙素和肿瘤坏死因子的影响[J].中国中西医结合杂志,1999;19(1):34-36.
    [55]肖长虹,顾为望,李留洋,等.类风湿性关节炎风寒湿痹与风湿热痹动物模型研究[J].中医杂志,1996;37(8):492-496.
    [56]肖长虹,顾为望,李留洋,等.类风湿性关节炎风寒湿痹与风湿热痹动物模型的病理研究[J].中国实验动物学报,1998;6(1):6-11.
    [57]徐世杰,肖诚,周桂琴,等.实验性脾虚痹证的黏膜免疫学机制研究[J].中国中医基础医学杂志,2003;9(12):35-38.
    [58]严健民.五十二病方注补译[M].北京:中国古籍出版社,2005:44-45.
    [59]Brownstein MJ.A brief history of opiates,opioid peptides,and opioid receptors[J].Proc Natl Acad Sci USA,1993;90(12):5391-5393.
    [60]刘威,段海清,张兆山.阿片受体的研究进展[J].生物技术通讯,2003;14(3):231-234.
    [61]金昔陆,池志强.阿片受体及其信号转导[J].中国药理学通报,1997;13(6):488-491.
    [62]王蕾,欧可群.内源阿片肽的研究进展[J].四川解剖学杂志,2000;8(4):227-230.
    [63]Evans CJ,Keith DE Jr,Morrison H,et al.Cloning of a delta opioid receptor by functional expression[J].Science,1992;258(5090):1952-1955.
    [64]Kieffer BL,Befort K,Gaveriaux-Ruff C,et al.The delta-opioid receptor:isolation of a cDNA by expression cloning and pharmacological characterization[J].Proc Natl Acad Sci USA,1992;89(24):12048-12052.
    [65]Chen Y,Mestek A,Liu J,et al.Molecular cloning and functional expression of a mu-opioid receptor from rat brain[J].Mol Pharmacol,1993;44(1):8-12.
    [66]Yasuda K,Raynor K,Kong H,et al.Cloning and functional comparison of kappa and delta opioid receptors from mouse brain[J].Proc Natl Acad Sci USA,1993;90(14):6736-6740.
    [67]Mollereau C,Parmentier M,Mailleux P,et al.ORL1,a novel member of the opioid receptor family.Cloning,functional expression and localization[J].FEBS Lett,1994:341(1):33-38.
    [68]Hughes J,Smith TW,Kosterlitz HW,et al.Identification of two related pentapeptides from the brain with potent opiate agonist activity[J].Nature,1975,18;258(5536):577-580.
    [69]Li CH,Lemaire S,Yamashiro D,et al.The synthesis and opiate activity of beta-endorphin[J].Biochem Biophys Res Commun,1976,12;71(1):19-25.
    [70]Ling N,Burgus R,Guillemin R.Isolation,primary structure,and synthesis of alpha-endorphin and gamma-endorphin,two peptides of hypothalamic-hypophysial origin with morphinomimetic activity[J].Proc Natl Acad Sci USA,1976,73(11):3942-3946.
    [71]Goldstein A,Tachibana S,Lowney LI,et al.Dynorphin-(1-13),an extraordinarily potent opioid peptide[J].Proc Natl Acad Sci USA,1979;76(12):6666-6670.
    [72]Reinscheid RK,Nothacker HP,Bourson A,et al.Orphanin FQ:a neuropeptide that activates an opioidlike G protein-coupled receptor[J].Science,1995;270(5237):792-794.
    [73]Meunier JC,Mollereau C,Toll L,et al.Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor[J].Nature.1995:377(6549):532-535.
    [74]韩济生.发现内阿片肤家族的两个新成员--孤啡肽和内吗啡肽[J].中国疼痛医学杂志.1997,3(3):129-134.
    [75]Zadina JE,Hackler L,.Ge LJ,et al.A potent and selective endogenous agonist for the mu-opiate receptor[J].Nature,1997,386(6624):499-502.
    [76]Qinyang W,Lindgren JU,Elhassan AM,et al.Distribution of leucine-enkephalin in bone and joint tissues[J].Neuropeptides,2002;36(4):281-286.
    [77]史玉兰.张金平,白文忠.脑啡肽的研究进展[J].河北医科大学学报,2007:28(2):148-150.
    [78]杨溢秦,郭丹,马敏,等.内源性阿片肽家族的结构特点和生理功能[J].南京军医学院学报,2002;24(2):102-103,106.
    [79]王玉秀,童昭岗,胡海青.内源性阿片肽系统免疫调节功能的研究进展[J].中国临床康复,2002;7(10):1158-1159.
    [80]Giuliani S,Tramontana M,Lecci A,et al.Effect of nociceptin on heart rate and blood pressure in anaesthetized rats[J].Eur J Pharmacol,1997;333(2-3):177-179.
    [81]Meunier JC.Nociceptin/orphanin FQ and the opioid receptor-like ORL1receptor[J].Eur J Pharmacol,1997;340(1):1-15
    [82]富歆,王彦青,吴根诚.内源性阿片样肽--内吗啡肽的研究进展[J].国外医学药学分册,2003:30(6):339-344.
    [83]Martin-Schild S,Gerall AA,Kastin AJ,et al.Differential distribution of endomorphin-1 and endomorphin-2 like immunoreactivities in the CNS of the rodent[J].J Comp Neurol,1999;405(4):450-471.
    [84]Millan MJ.Descending control of pain[J].Prog Neurobiol,2002:66(6):355-474.
    [85]吴根诚,王彦青,朱崇斌,等.孤啡肽(OFQ)参与痛觉调制和针刺镇痛及其中枢机制[J].医学研究通讯,2002;31(10):19-20.
    [86]李辉,李云庆.内源性阿片肽参与痛信息调控的机制[J].神经解剖学杂志,2004;20(2):191-196.
    [87]V Euler US,Gaddum JH.An unidentified depressor substance in certain tissue extracts[J].J Physiol,1931;72(1):74-87.
    [88]龚乐亭.生物活性肽--结构与功能[M].上海:科技出版社,1985:160-165.
    [89]李淑梅,赵文爱,胡圣爱.P物质的研究概况[J].医学动物防制,1999;15(5):278-280.
    [90]Chang MM,Leeman SE,Niall HD.Amino-acid sequence of substance P[J].Nat New Biol,1971;232(29):86-87.
    [91]Tregear GW,Niall HD,Ports JT Jr,et al.Synthesis of substance P[J].Nat New Biol,1971;232(29):87-89.
    [92]李伟红,姜恩魁.P物质的研究现状[J].锦州医学院学报,1999;20(2):64-67.
    [93]Schenker C,Mroz EA,Leeman SE.Release of substance P from isolated nerve endings[J].Nature,1976;264(5588):790-792.
    [94]Otsuka M,Konishi S.Substance P and excitatory transmitter of primary sensory neurons[J].Cold Spring Harb Symp Quant Biol,1976;40:135-143.
    [95]王丽凤,张尚俭,司军强,等.P物质在非中枢神经系统中的作用[J].石河子大学学报(自然科学版),2003;7(4):336-340.
    [96]De Koninck Y,Ribeiro-da-Silva A,Henry JL,et al.Spinal neurons exhibiting a specific nociceptive response receive abundant substance P-containing synaptic contacts[J].Proc Natl Acad Sci USA,1992;89(11):5073-5077
    [97]闰国平,赵晏.P物质参与痛觉调控的研究进展[J].国外医学生理、病理科学与临床分册,1996;16(3):196-198.
    [98]周武庆,李义梅,法祥光.P物质与炎症研究进展[J].国外医学免疫学分册,1997;(2):959-8.
    [99]孙宏伟,任广睦,高彩荣.P物质与炎性疾病研究进展[J].山西医科大学学报,2005;36(2):257-260.
    [100]Warsame Afrah A,Gustafsson H,Olgart L,et al.Capsaicin-evoked substance P release in rat dorsal horn increases after poripheral inflammation:a microdialysis study[J].Neurosci Lett,2004;368(2):226-230.
    [101]王秀梅,沈敬华.类风湿关节炎与细胞因子[J].内蒙古医学杂志,2007;39(3):330-332.
    [102]金惠铭,卢建,殷莲华.细胞分子病理生理学[M].郑州:郑州大学出版社,2002:110-126.
    [103]金伯泉.现代细胞与分子免疫学[M].第2版,北京:科学出版社,2001:104-119.
    [104]柏干苹,方勇飞.细胞因子与类风湿性关节炎[J].临床内科杂志,2001;18(4):257-259.
    [105]Weyand CM,McCarthy TG,Goronzy JJ.Correlation between disease phenotype and genetic heterogeneity in rheumatoid arthritis[J].J Clin Invest,1995;95(5):2120-2126.
    [106]Fassbender HG.What destroys the joint in rheumatoid arthritis?[J].Arch Orthop Trauma Surg,1998;117(1-2):2-7.
    [107]Gery I,Gershon RK,Waksman BH.Potentiation of cultured mouse thymocyte responses by factors released by peripheral leucocytes[J].J Immunol,1971;107(6):1778-1780.
    [108]郭甫坤,凌世淦.白细胞介素-1结构与功能关系的研究进展[J].国外医学分子生物学分册,1997;19(5):216-219.
    [109]Athanasou NA.Synovial macrophages[J].Ann Rheum Dis,1995;54(5):392-394.
    [110]Arend WP,Bayer JM.Cytokines and cytokine inhibitors or antagonists in rheumatoid arthritis[J].Arthritis Rheum,1990;33(3):305-315.
    [111]Tyler JA.Chondrocyte-mediated depletion of articular cartilage proteoglycans in vitro[J].Biochem.J,1985;225(2):493-507.
    [112]Tyler JA.Articular cartilage cultured with catabolin(pig interleukin 1)synthesizes a decreased number of normal proteoglycan molecules[J].Biochem J,1985;227(3):869-878.
    [113]Lack CH,Rogers HJ.Action of plasmin on cartilage[J].Nature,1958;182(4640):948-949.
    [114]柏干苹,方勇飞.细胞因子与类风湿性关节炎[J].临床内科杂志,2001;18(4):257-259.
    [115]Carswell EA,Old LJ,Kassel RL,et al.An endotoxin-induced serum factor that causes necrosis of tumors[J].Proc Natl Acad Sci USA,1975;72(9):3666-3670.
    [116]Vassalli P.The pathophysiology of tumor necrosis factors[J].Annu Rev Immunol,1992;10:411-452.
    [117]贺立文,祝家镇.肿瘤坏死因子的研究进展[J].中国法医学杂志,1997:12(2):122-124.
    [118]史宇晖,刘树贤,王育.肿瘤坏死因子研究进展[J]。河北医科大学学报,1998;19(4):249-252.
    [119]Dayer JM,Beutler B,Cerami A.Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts[J].J Exp Med,1985:162(6):2163-2168.
    [120]Peacock DJ,Banquerigo ML,Brahn E.Angiogenesis inhibition suppresses collagen arthritis[J].J Exp Med,1992;175(4):1135-1138.
    [121]Mφlvig J,Baek L,Christensen P,et al.Endotoxin-stimulated human monocyte secretion of interleukin 1,tumour necrosis factor alpha,and prostaglandin E2 shows stable interindividual differences[J].Scand J Immunol,1988;27(6):705-716.
    [122]Seckinger P,Isaaz S,Dayer JM.A human inhibitor of tumor necrosis factor alpha[J].J Exp Med,1988;167(4):1511-1516.
    [123]蔡青,孟济明.IL-1和TNF与类风湿性关节炎[J]。上海免疫学杂志,1998;18(1):62-63.
    [124]Hirano T,Yasukawa K,Harada H,Taga T et al.Complementary DNA for a novel human interleukin(BSF-2) that induces B lymphocytes to produce immunoglobulin[J].Nature,1986;324(6092):73-76.
    [125]任蕴芳,唐佩弦.白细胞介素6研究进展[J]。解放军医学情报,1992;6(4):195-197.
    [126]刘军才,李鹰.白细胞介素-6的研究进展[J].牡丹江医学院学报,1998;19(1):38-40。
    [127]汤慧华,冯忠军,郭晓华,等.IL-6及TNF-α在类风湿关节炎免疫发病机制中的作用[J].中华风湿病学杂志,1998;2(4):236-238.
    [128]Morgan DA,Ruscetti FW,Gallo R.Selective in vitro growth of T lymphocytes from normal human bone marrows[J].Science,1976;193(4257):1007-1008.
    [129]郑建华.白介素-2研究进展[J].海峡药学,2006;18(4):1-3.
    [130]苏涛,王克超,陈检芳,等。类风湿性关节炎患者血清IL-2,TNF和CRP含量变化与临床意义[J].中国医学工程,2005;13(3):247-248.
    [131]Fiorentino DF,Bond MW,Mosmann TR.Two types of mouse T helper cell.IV.Th2clones secrete a factor that inhibits cytokine produqtion by Th1 clones[J].J Exp Med,1989;170(6):2081-2095.
    [132]王辉,孟庆华。白细胞介素-10研究进展[J].继续医学教育,2007,21(32):58-62.
    [133]高俊,丁真奇.细胞因子在类风湿性关节炎中作用的研究现状[J].医学综述,2006;12(5):289-291。
    [134]Moore KW,de Waal Malefyt R,Coffman RL,et al.Interleukin-10 and the interleukin-10 receptor[J].Annu Rev Immunol,2001;19:683-765.
    [135]Min SY,Hwang SY,Park KS,et al.Induction of IL-10-producing CD4+CD25+ T cells in animal model of collagen-induced arthritis by oral administration of type Ⅱ collagen[J].Arthritis Res Ther,2004;6(3):R213-219.
    [136]刘家琴,蔡鋆,陈崇华.风湿与类风湿性关节炎IgG、IgE测定及临床意义[J].江苏医药,1995;21(1):57-58.
    [1]秦林,彭欣.论寒热配伍在痹证治疗中的意义[J]。中国中药杂志1999,24(2):112.
    [2]李晋奇,王岚,彭成.川乌配伍白芍的现代临床应用与药理研究浅析[J].中医药学刊,2003;21(12):2103-2104。
    [3]刘兴旺。大葛根汤治疗痹证200例临床分析[J].山西中医,1992;8(6):17.
    [4]徐桂荣,桑亚雄,徐德茄.益肾温经通痹汤治疗沤痹60例[J].光明中医杂志,1995;(3):52-54。
    [5]张跃传.乌头汤加减治疗痹证100例临床观察[J].河南中医,1996;16(4):214.
    [6]范希进.自拟秦艽乌头汤治疗痹证378例[J].中医药研究,1999;15(5):21-22.
    [7]孔维平.乌头汤加减治疗风寒湿痹45例体会[J]。云南中医中药杂志,2002;23(2):28.
    [8]杜天信,任汉阳,李根林.寒湿痹片治疗寒湿痹阻型风湿病的临床观察[J]。中医正骨,2002:14(8):5-7.
    [9]毛玉安.调和营卫治疗痹证180例[J].中国民间疗法,2004;12(2):45-46.
    [10]李裕怀.乌头汤加味治慢性腰腿痛50例临床观察[J].江西中医药,1995;(增刊):112.
    [11]朱学芳.乌头汤加减治疗腰腿痛[J].湖北中医杂志,1997;19(4):37。
    [12]罗湘筠.针药结合治疗寒湿型急性腰腿痛60例临床观察[J].湖南中医药导报,2004:10(7):58-59.
    [13l程功华.乌头汤治疗慢性腰腿痛56例[J].实用中医内科杂志,2005:19(5):455.
    [14]张文生,邹忆怀,谢颖桢,等.中医综合康复疗法治疗中风偏瘫痉挛状态60例临床观察[J].中医杂志,2000;41(12):723-725.
    [15]勾廷祥,阴公举,勾德铭,等.乌头汤治类风湿性关节炎42例[J].国医论坛,1996:11(1):20.
    [16]路绪文,刘子江,李金更.痹通胶囊治疗类风湿性关节炎118例临床观察[J].实用中医药杂志,1996;(4):3-4.
    [17]王绍海.乌头汤加味治疗类风湿性关节炎[J].天津中医学院学报,2000.03.15;19(1):26-27.
    [18]张太峰,万强,李薇,等.消风除湿胶囊治疗类风湿性关节炎48例临床观察[J].天津中医,2002;19(1):1-416.
    [19]刘学义,俞平.桂枝芍药知母汤治疗类风湿性关节炎83例[J]。贵阳中医学院学报,2003;25(4):23-24.
    [20]何煜舟,温成平,曹灵勇,等.桂乌汤治疗类风湿性关节炎临床观察[J].浙江中西医结合杂志,2005:15(5):269-270.
    [21]孙义军,宋国昱,种清智,等.中药雾化加鸡矢藤注射液治疗类风湿性关节炎36例[J].陕西中医学院学报,2005;28(2):23-24。
    [22]董顺明.补气活血祛风汤治疗活动性类风湿性关节炎52例[J].辽宁中医学院学报,2006;8(2):70-71.
    [23]胡卫东,林昌松,孔德奇,等.加味桂枝芍药知母汤对类风湿性关节炎患者生存质量干预的研究[J].中国中医药信息杂志,2007;14(4):14-16.
    [24]吴长忠,许卫军.中西医结合三联法治疗类风湿性关节炎阴虚络热证40例[J].中医杂志,2007;48(8):705-706,709.
    [25]陈立富.增效乌头汤治疗腰椎间盘突出症105例[J].河北中医,1995;17(1):27-28.
    [26]曹建雄,张杏坤.利腰蠲痹汤内服消痞镇痛膏外敷治疗腰椎及腰椎间盘退行性病变49例[J].中医药信息,1998;(3):43-44.
    [27]钱邦平.加味乌头汤内服配合牵引治疗腰椎间盘突出症[J].新疆中医药,2000:18(2):25-26
    [28]林建伦,李玉贞,李凤兰,等.归芪乌头汤、治伤消瘀丸内服加娄峰正骨膏外敷治疗腰 椎间盘突出症的临床研究[J].现代医院,2005;5(4):13-15.
    [29]万全庆.活血搜风法合针刀治疗颈椎间盘突出症120例[J].浙江中西医结合杂志,2007;17(11):718-719.
    [30]龙国田.乌头蠲痹汤治疗肩关节周围炎75例[J].湖南中医药导报,1995;1(5):41-42.
    [31]吴春.当归四逆汤加味治疗冻结肩55例体会[J]。现代中西医结合杂志,1999;8(9):1468-1469.
    [32]李学祥,李军,曹文辉,等.葛根乌头汤治疗肩周炎108例观察[J].实用中医药杂志,2000;16(6):11。
    [33]苏再安,方承康.舒肩汤结合功能煅炼治疗顽固性肩周炎47例[J]。实用中医药杂志,2005;21(3):155。
    [34]蔡东升,钟邦琴.针刀闭合松解术加中药内服治疗肩周炎疗效观察[J].湖北中医杂志,2006;28(11):47-48.
    [35]杨少波,刘绪银.葛芍艽仙四虫散加减治疗颈椎病112例临床观察[J]。中医药导报,2005;11(4):46-48.
    [36]陈灼彬.中西医结合治疗颈椎病38例临床观察[J].中医药导报,2006;12(8):41-42.
    [37]周保定,王华,华敬,等。中西医结合治疗神经根型颈椎病35例[J].国医论坛,2007:22(3):44-45.
    [38]戴朝寿,贺秀莲.乌头桂枝汤治疗强直性脊柱炎89例[J].国医论坛1996.03.20;11(2):16
    [39]李建松,张静,林昌松,等.通痹灵治疗强直性脊柱炎临床疗效评价[J]。临床医药实践杂志,2007;16(6):453-455.
    [40]詹学斌,詹强.自拟活血补肾通络汤治疗脊柱骨质增生综合征70例[J].上海中医药杂志,1996;(3):23
    [41]张清,刘绪银.葛芍艽仙四虫散治疗脊椎骨质增生症109例[J].湖南中医药导报,1996;2(6):23-24.
    [42]周岳君。中药熏洗结合推拿治疗膝关节退行性病变61例[J].浙江中医杂志,1998:33(12):560.
    [43]种清治,种清云.手法加中药治疗膝关节退行性骨关节病156例临床体会[J].陕西中医学院学报,2001;24(2):27-28.
    [44]郑湘宏,陈翠环,黄霖.活络止痛片治疗膝关节退行性骨关节炎临床观察[J].中国中医急症,2005:14(5):433,452.
    [45]陈邦芝.细辛乌头汤治疗坐骨神经痛52例[J].辽宁中医杂志,1995:22(7):318.
    [46]杨茂丁,赵玉明.乌蝎汤治疗原发性坐骨神经痛42例[J].四川中医,1995:13(9):29.
    [47]沈允浩。《金匮》乌头汤加味治疗坐骨神经痛36例[J].江西中医药,1995:(增刊):67-68。
    [48]杨继新.风湿敌治疗坐骨神经痛39例[J].湖北中医杂志,1996:18(1):46.
    [49]李昌荣.乌头汤治疗坐骨神经痛[J]。中医药研究,1997;13(1):27.
    [50]梁惠贞.陈汉礼.中药除痹通络汤治疗坐骨神经痛68例[J].广州医药,2004;35(3):75-76.
    [51]陈付合.自拟阳和三乌汤治疗坐骨神经痛62例[J].国医论坛,2007:22(5):33。
    [52]刘国昌.乌头汤治疗三叉神经痛24例[J].中医药学报1995.12.20:(6):31
    [53]白光辉,张建华.加减乌头汤治疗三叉神经痛28例[J].现代中西医结合杂志,2003;12(4):385.
    [54]魏铁花,刘明芳,于洋.愈痛散胶囊治疗偏头痛90例[J]。中医药学报。2005:33.(5):43.
    [55]朱书营.天麻通络胶囊配芍药甘草汤治疗血管神经性头痛63例[J].河南中医学院学报,2007;22(1):65.
    [56]黄再军.综合疗法治疗眼肌型重症肌无力[J].按摩与导引,1996:(1):25-26.
    [57]张敏.中西医结合治疗单纯性眼肌型重症肌无力[J].河南中医,1997;17(5):297-298.
    [58]郗西军,姚登强.乌头防己汤治疗膝关节囊积液37例[J].内蒙古中医药,1997;16(2):8.
    [59]蒋四清,徐昌伟.手法配合中药治疗梨状肌综合征38例[J].湖北中医杂志,2000:22(1):46.
    [60]张守胜,胡艳敏.乾坤康复液为主治疗腹腔粘连96例[J]。新中医,2000:32(6):29。
    [61]张建军.芍药钩藤木耳汤加味治疗面神经麻痹56例疗效观察[J].内蒙古中医药,2002;(3):3.
    [62]霍玉芳,于慧卿。百合丹参芍药汤治疗上消化道溃疡200例临床观察[J].河北中医,1996;18(6):11
    [63]许方方,俞永湘。加减五倍子汤治疗痔瘘科疾病238例报告[J].安徽中医临床杂志,2000;12(3):201-202.
    [64]何伟,王宁,秦林,等.川乌与白芍配伍前后乌头碱和芍药苷煎出量的测定[J].中国药学杂志,2002:37(9):680-683.
    [65]余成浩,彭成,余葱葱,等.制川乌配伍白芍不同配伍比例对酯型生物碱含量的影响[J].都中医药大学学报,2007;30(4):43-45.
    [66]张少华,彭欣,秦林,等.乌-芍及乌-防配伍前后对实验性疼痛的影响[J].中草药,1999:30(8):595-598.
    [67]秦林,彭欣,李晓丽,等.川乌配伍白芍对实验性疼痛的影响[J].中国中药杂志,1999;24(10):629-632.
    [68]秦株,彭欣,张勤生,等.剂量变化对川乌配伍白芍镇痛作用的影响[J].山东中医药大学学报,1999;23(4):225-227.
    [69]李晋奇,彭成。制川乌配伍白芍的增效作用及其作用机理[J]。华西药学杂志,2007:22 (2):144-148.
    [70]张惠云,秦林,薛玲,等。川乌与白芍配伍前后抗炎作用的比较研究[J].山东中医药大学学报,2000:24(4):29-7300.
    [71]张惠云,秦林,薛玲,等.川乌配伍白芍的抗炎作用特点研究[J]。中国中药杂志,2002;27(6):449-452.
    [72]薛玲,张惠云,秦林,等.川乌与白芍配伍前后对大鼠佐剂性关节炎的影响[J].中国中药杂志,2000:25(3):175-176.
    [73]秦林,彭欣,张少华,等.川乌配伍白芍对炎症因子及自由基的影响[J].中国中药杂志,2000;25(6):370-373.
    [74]张育,薛永骥,梁虹,等.乌芍制剂对关节炎大鼠抗风湿机制的实验研究[J].时珍国医国药,2003;14(7):f3-f4。
    [75]秦林,张少华,李晓丽,等.川乌与白芍配伍的免疫调节作用初探[J].中国中药杂志,2002;27(7):541-544.
    [76]秦林,彭欣,李晓丽,等.白芍与川乌配伍前后急性毒性实验研究[J].山东中医药大学学报,2000;24(6):453-455.
    [1]王绪辉,郑效文,施杞.肢体痹证的造模方法[J].上海中医药杂志,1986:(3):3-5.
    [2]王绪辉,朱显华,周恩元,等.风湿寒性关节痛实验模型及病理学研究[J].中医杂志,1990;(7):50-52.
    [3]徐成林,钟尧舜,宋举武.痹证动物模型研究-风寒湿对家兔关节的影响[J].新疆中医药,1989;(4):12-13,11。
    [4]吕爱平,王安民,曾晓莲.益肾蠲痹丸对大鼠实验性痹证影响的病理学研究[J].中华中医骨伤科杂志,1988;4(6):49-51。
    [5]吕爱平,艾景录,冀向东,等.大鼠肌腱和肌肉在实验性痹证中的病理学改变[J].中国骨伤,1993:6(3):7-8.
    [6]艾景录,吕爱平,徐世杰,等.性腺动能异常型肾虚痹证发生机理的实验研究[J].中国中医基础医学杂志,1995:1(1):42-44.
    [7]徐世杰,吕爱平,张春英,等.切除卵巢所致肾虚对Ⅱ型胶原诱导的关节炎小鼠IL-2和IL-6含量的影响[J].中国中医基础医学杂志,1998;4(10):33-35.
    [8]徐世杰,吕爱平,王安民,等。切除卵巢所致肾虚对免疫性关节炎小鼠血清钙素和肿瘤坏死因子的影响[J].中国中西医结合杂志,1999;19(1):34-36.
    [9]肖长虹,顾为望,李留洋,等.类风湿性关节炎风寒湿痹与风湿热痹动物模型研究[J].中医杂志,1996:37(8):492-496.
    [10]肖长虹,顾为望,李留洋,等.类风湿性关节炎风寒湿痹与风湿热痹动物模型的病理研 究[J].中国实验动物学报,1998:6(1):6-11.
    [11]金祝秋,郑建生,彭芝配,等.大鼠风寒湿痹证模型的建立与前列腺素E2的关系[J].湖南中医学院学报,1996;16(1):40-42.
    [12]李晋奇,彭成.制川乌配伍白芍的增效作用及其作用机理.华西药学杂志,2007;22(2):144-148.
    [13]徐世杰,肖诚,周桂琴,等。实验性脾虚痹证的黏膜免疫学机制研究[J]。中国中医基础医学杂志,2003;9(12):35-38.
    [14]Pearson CM,Wood FD.Studies of polyarthritis and other lesions induced in rats by injection of mycobacterial adjuvant,I.General clinical and pathologic characteristics and some modifying factors[J].Arthritis Rheum 1959;2:440-459
    [15]Trentham DE,Townes AS,KangAH.Autoimmunity to type Ⅱcollagen an experimental model of arthritis[J].J Exper Med.1977;146(3):857-868
    [16]王春田,于静.类风湿关节炎动物模型研究进展[J].辽宁中医杂志,2003;30(6):511-512.
    [17]李伟,张远强,刘新平,等.佐剂型类风湿关节炎模型改良与DDR2表达的研究[J].中国组织化学与细胞化学杂志,2003;12(1):89-93.
    [18]力弘,贾永锋,潘雁,等.Ⅱ型胶原蛋白诱导的类风湿性关节炎的动物模型[J].上海医科大学学报,1997;24(3):231-233.
    [19]Mc Cartney-Francis N,Allen JB,Mizel DE,et al.Suppression of arthritis by an inhibitor,of nitric oxide synthase[J].J Exp Med,1993;1178(8):749-754.
    [20]Coderre TJ,Wall PD.Ankle joint arthritis in rats:an alternative animal model of arthritis to that produced by Freud' s adjuvant[J].Pain,1987;28:379-393.
    [21]Coderre TJ,Wall PD.Ankle joint arthritis in rats provides a useful tool for the evaluation of analgesic and anti-arthritic agents[J].Pharm Biochem Behav,1988;29(3):461-463.
    [22]高铁祥,赵婷秀,游秋云,等.痛风康片治疗痛风的实验研究[J].中国中医药科技,2002;9(1):17-18.
    [23]陈文照,姜宏,刘延龄.痛风宁消炎镇痛的实验研究[J].中国中医骨伤科杂志,1999;7(4):1-3.
    [24]黄火高,孙运峰,胡明,等.大鼠急性痛风性关节炎模型的建立及特点[J].军事医学科学院院刊,2005;29(6):538-542.
    [25]Wu X,Wakamiya M,Vaishnav S,et al.Hyperuricemia and urate oxidese-deficient mice[J].Proc Natl Acad Sci USA,1994:91(2):742.
    [26]张超,曹克光,杨崇青,等.高尿酸血症及尿酸性肾病动物模型的建立及应用[J].实验动物科学与管理,1999;16(4):18-22.
    [27]苏友新,陈伟宏,王和鸣,等.痛风宁颗粒对实验性鸡痛风性关节炎的影响[J].中国骨 伤,2003:16(5):275-277.
    [28]曹克光,臧力学,唐丽,等.高尿酸血症动物模型的建立及应用[J].实验动物科学与管理,2000,17(2):6-9.
    [29]刘小青,张冰,刘春梅.鹌鹑高尿酸血症模型建立初探[J].中国病理生理杂志,2001;17(10):1038-1040.
    [30]唐灿,杨奎.高尿酸血症动物模型初探[J]。中药新药与临床药理,2000,11(5):292-294.
    [31]陈光亮,张清林,马晓芹,等.酵母致小鼠高尿酸血症模型[J].中国药理学通报,2003:19(4):467-479。
    [32]陈光亮,孙秀霞,王钦茂等.小鼠高尿酸血症模型的研究[J].中国药理学通报,2001;17(3):350-352。
    [33]奚九一,赵兆琳,鲁培基,等.高尿酸血症的实验动物模型研究[J].上海中医药杂志,2001:(10):10-12.
    [34]喻志峰,杨澄,仇熙,等瑞香苷对高尿酸血症小鼠的影响[J].中国药科大学学报,2002;33(2):142-145.
    [35]Iris HH,John PS,David JR,et al.Substituted cyclic imides as potencial ant i-gout-agents[J].Life Sci,1990;46(26):1923- 1927.
    [36]熊湘明,曲竹秋.大鼠高尿酸血症模型建立[J].天津中医学院学,2001;20(4):28-29.
    [37]金沈锐,郑军,刘绍唐.实验动物模型研究小鼠高尿酸血症模型初探[J].成都中医药大学学报,1999;22(1):49-50,64。
    [38]徐立,时乐.小鼠代谢性高尿酸血症模型的复制方法初探[J].中国比较医学杂志,2006:16(1):1-4.
    [39]徐立,时乐,赵芳,等.大鼠急性高尿酸血症模型的复制方法初探[J].中国药理学通报,2007;23(7):976-978.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700