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研究生:陳芳玉
研究生(外文):Fang Yu Chen
論文名稱:龍膽瀉肝湯對紅斑性狼瘡小鼠CD4+CD25+T細胞免疫調控機制之研究
論文名稱(外文):Immunomodulation of Longdan-Xiegan-Tang on CD4+CD25+ T Cell in MRL lpr/lpr Mice
指導教授:李宗諺李宗諺引用關係
指導教授(外文):T. Y. Lee
學位類別:碩士
校院名稱:長庚大學
系所名稱:傳統中國醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
論文頁數:95
中文關鍵詞:龍膽瀉肝湯CD4+CD25+T細胞系統性紅斑性狼瘡抗氧化
外文關鍵詞:Longdan Xiegan TangCD4+CD25+ T cellsystemic lupus erythematosusAntioxidants
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龍膽瀉肝湯是中醫臨床最常用的清熱瀉火劑之一。過去研究發現中藥方劑龍膽瀉肝湯具有抗發炎、保肝及免疫刺激等效用。在本實驗中,以MRL lpr/lpr小鼠為自發性自體免疫疾病動物模式,小鼠在生長的過程中會出現類似人類全身性紅斑性狼瘡的症狀,探討MRL lpr/lpr小鼠給予龍膽瀉肝湯餵食後出現的生理反應。於第19週大隨機分組,實驗組小鼠給予龍膽瀉肝湯(250mg/kg) ,每天一次經由胃管連續餵食二週。收集血液、脾臟與腎臟組織進行病理檢驗與免疫分析。實驗結果發現,MRL lpr/lpr小鼠呈現明顯脾臟腫大的現象,龍膽瀉肝湯治療組的小鼠脾臟明顯縮小,我們分析這作用與脾臟中CD3+CD4+、CD3+CD8+及CD4+CD25+T細胞的增加情形有關。龍膽瀉肝湯介入MRL lpr/lpr小鼠治療,顯著降低血中Anti-dsDNA、TNF-α與IFN-γ的濃度,並可增加腎臟組織內GSH的含量及減少iNOS及COX-2蛋白質表現,進而降低MRL lpr/lpr小鼠體內的氧化壓力及緩解發炎情形,也確實改善了MRL lpr/lpr小鼠外觀脫毛潰爛發炎的現象。龍膽瀉肝湯也改善MRL lpr/lpr小鼠嚴重的腎膈增生情形,腎臟組織IgG染色沉積也較MRL組輕微。蛋白質體研究結果發現,龍膽瀉肝湯對於緩解MRL lpr/lpr小鼠疾病嚴重度可能是透過增加腎臟組織裡的phosphoglycerate kinase 1蛋白質的表現並降低ferritin light chain 1、selenium-binding protein 2及alpha-enolase等蛋白質的表現。
本研究結果顯示,龍膽瀉肝湯降低紅斑性狼瘡小鼠體內氧化壓力與減緩疾病嚴重度有密切關係。
Longdan Xiegan Tang (LXT) is a Chinese herbal medicine that is prescribed as an anti-inflammatory aid, a hepato-protectant, and an immunostimulant. In this study, we examined the biological effects of LXT administration in MRL/lpr mice.
MRL/lpr mice develop immunological disturbances and deregulated production of Th1 and Th2 cytokines and are a good model of systemic lupus erythematosus (SLE). Female MRL/lpr mice were randomly separated into two groups. The experimental group received LXT (250 mg/kg/day, po) from 19 to 21 weeks of age. At 21 weeks of age, the animals were euthanized and kidneys and spleens were removed for evaluation. Splenic CD3+CD4+, CD3+CD8+, and CD4+CD25+ T cells were increased in the LXT-administered mice compared to MRL/lpr controls, and this was associated with splenomegaly.
There was a marked reduction in IFN-, TNF-, anti-dsDNA antibody, and there were reduced IgG immune complex deposits in the glomeruli. LXT also restored kidney glutathione levels, thereby limiting the toxic effects of the inflammatory mediators iNOS and COX-2, which are overproduced in MRL/lpr mice. Two-dimensional gel electrophoresis was used to analyze proteome changes. LXT protected MRL/lpr mice against developing the lupus syndrome through up-regulation of phosphoglycerate kinase 1 and down-regulation of ferritin light chain 1, selenium-binding protein 2, and alpha-enolase, which were identified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry.
This study indicates that LXT at this dose and time course of administration was effective in reducing oxidative stress associated with disease progression in MRL/lpr mice. LXT could be useful as adjunctive therapy for reducing distress in SLE.
中文摘要 I
ABSTRACT II
縮寫對照表 IV
目錄 VI
第一章緒論 1
第二章 研究目的 25
第三章 實驗材料和方法 26
第四章 結果 41
第五章 討論 44
第六章 結論 49
參考文獻 50
圖表附錄 63
[1] P.J. Maddison, Is it SLE? Best Pract Res Clin Rheumatol 16 (2002) 167-80.
[2] I. Haq, and D.A. Isenberg, How does one assess and monitor patients with systemic lupus erythematosus in daily clinical practice? Best Pract Res Clin Rheumatol 16 (2002) 181-94.
[3] M.C. Hochberg, Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40 (1997) 1725.
[4] M. Petri, and L. Magder, Classification criteria for systemic lupus erythematosus: a review. Lupus 13 (2004) 829-37.
[5] B.L. Kotzin, Systemic lupus erythematosus. Cell 85 (1996) 303-6.
[6] C.C. Mok, and C.S. Lau, Pathogenesis of systemic lupus erythematosus. J Clin Pathol 56 (2003) 481-90.
[7] M.G. Robson, and M.J. Walport, Pathogenesis of systemic lupus erythematosus (SLE). Clin Exp Allergy 31 (2001) 678-85.
[8] M. Galeazzi, G.D. Sebastiani, G. Morozzi, C. Carcassi, G.B. Ferrara, R. Scorza, R. Cervera, E. de Ramon Garrido, A. Fernandez-Nebro, F. Houssiau, A. Jedryka-Goral, G. Passiu, C. Papasteriades, J.C. Piette, J. Smolen, G. Porciello, and R. Marcolongo, HLA class II DNA typing in a large series of European patients with systemic lupus erythematosus: correlations with clinical and autoantibody subsets. Medicine (Baltimore) 81 (2002) 169-78.
[9] L. Casciola-Rosen, and A. Rosen, Ultraviolet light-induced keratinocyte apoptosis: a potential mechanism for the induction of skin lesions and autoantibody production in LE. Lupus 6 (1997) 175-80.
[10] G.S. Cooper, C.G. Parks, E.L. Treadwell, E.W. St Clair, G.S. Gilkeson, P.L. Cohen, R.A. Roubey, and M.A. Dooley, Differences by race, sex and age in the clinical and immunologic features of recently diagnosed systemic lupus erythematosus patients in the southeastern United States. Lupus 11 (2002) 161-7.
[11] D. Verthelyi, M. Petri, M. Ylamus, and D.M. Klinman, Disassociation of sex hormone levels and cytokine production in SLE patients. Lupus 10 (2001) 352-8.
[12] K.D. Moudgil, and E.E. Sercarz, Dominant determinants in hen eggwhite lysozyme correspond to the cryptic determinants within its self-homologue, mouse lysozyme: implications in shaping of the T cell repertoire and autoimmunity. J Exp Med 178 (1993) 2131-8.
[13] D.I. Daikh, B.K. Finck, P.S. Linsley, D. Hollenbaugh, and D. Wofsy, Long-term inhibition of murine lupus by brief simultaneous blockade of the B7/CD28 and CD40/gp39 costimulation pathways. J Immunol 159 (1997) 3104-8.
[14] D. Wofsy, and W.E. Seaman, Successful treatment of autoimmunity in NZB/NZW F1 mice with monoclonal antibody to L3T4. J Exp Med 161 (1985) 378-91.
[15] A. Csiszar, G. Nagy, P. Gergely, T. Pozsonyi, and E. Pocsik, Increased interferon-gamma (IFN-gamma), IL-10 and decreased IL-4 mRNA expression in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 122 (2000) 464-70.
[16] G.S. Dean, J. Tyrrell-Price, E. Crawley, and D.A. Isenberg, Cytokines and systemic lupus erythematosus. Ann Rheum Dis 59 (2000) 243-51.
[17] A.N. Theofilopoulos, and B.R. Lawson, Tumour necrosis factor and other cytokines in murine lupus. Ann Rheum Dis 58 Suppl 1 (1999) I49-55.
[18] J.E. Salmon, S. Millard, L.A. Schachter, F.C. Arnett, E.M. Ginzler, M.F. Gourley, R. Ramsey-Goldman, M.G. Peterson, and R.P. Kimberly, Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans. J Clin Invest 97 (1996) 1348-54.
[19] R. Licht, J.W. Dieker, C.W. Jacobs, W.J. Tax, and J.H. Berden, Decreased phagocytosis of apoptotic cells in diseased SLE mice. J Autoimmun 22 (2004) 139-45.
[20] G. Filaci, S. Bacilieri, M. Fravega, M. Monetti, P. Contini, M. Ghio, M. Setti, F. Puppo, and F. Indiveri, Impairment of CD8+ T suppressor cell function in patients with active systemic lupus erythematosus. J Immunol 166 (2001) 6452-7.
[21] M. Linker-Israeli, F.P. Quismorio, Jr., and D.A. Horwitz, CD8+ lymphocytes from patients with systemic lupus erythematosus sustain, rather than suppress, spontaneous polyclonal IgG production and synergize with CD4+ cells to support autoantibody synthesis. Arthritis Rheum 33 (1990) 1216-25.
[22] E. Cadenas, Mitochondrial free radical production and cell signaling. Mol Aspects Med 25 (2004) 17-26.
[23] P.R. Ames, J. Alves, I. Murat, D.A. Isenberg, and J. Nourooz-Zadeh, Oxidative stress in systemic lupus erythematosus and allied conditions with vascular involvement. Rheumatology (Oxford) 38 (1999) 529-34.
[24] I.E. Bultink, T. Teerlink, J.A. Heijst, B.A. Dijkmans, and A.E. Voskuyl, Raised plasma levels of asymmetric dimethylarginine are associated with cardiovascular events, disease activity, and organ damage in patients with systemic lupus erythematosus. Ann Rheum Dis 64 (2005) 1362-5.
[25] S. Sakaguchi, N. Sakaguchi, M. Asano, M. Itoh, and M. Toda, Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 155 (1995) 1151-64.
[26] S. Read, S. Mauze, C. Asseman, A. Bean, R. Coffman, and F. Powrie, CD38+ CD45RB(low) CD4+ T cells: a population of T cells with immune regulatory activities in vitro. Eur J Immunol 28 (1998) 3435-47.
[27] A.M. Thornton, and E.M. Shevach, CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 188 (1998) 287-96.
[28] D. Dieckmann, H. Plottner, S. Berchtold, T. Berger, and G. Schuler, Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med 193 (2001) 1303-10.
[29] H. Jonuleit, E. Schmitt, M. Stassen, A. Tuettenberg, J. Knop, and A.H. Enk, Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J Exp Med 193 (2001) 1285-94.
[30] L.A. Stephens, and D. Mason, CD25 is a marker for CD4+ thymocytes that prevent autoimmune diabetes in rats, but peripheral T cells with this function are found in both CD25+ and CD25- subpopulations. J Immunol 165 (2000) 3105-10.
[31] L.A. Stephens, C. Mottet, D. Mason, and F. Powrie, Human CD4(+)CD25(+) thymocytes and peripheral T cells have immune suppressive activity in vitro. Eur J Immunol 31 (2001) 1247-54.
[32] E.M. Shevach, CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol 2 (2002) 389-400.
[33] A.M. Thornton, E.E. Donovan, C.A. Piccirillo, and E.M. Shevach, Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function. J Immunol 172 (2004) 6519-23.
[34] J. Shimizu, S. Yamazaki, T. Takahashi, Y. Ishida, and S. Sakaguchi, Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 3 (2002) 135-42.
[35] R.S. McHugh, M.J. Whitters, C.A. Piccirillo, D.A. Young, E.M. Shevach, M. Collins, and M.C. Byrne, CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 16 (2002) 311-23.
[36] F. Lepault, and M.C. Gagnerault, Characterization of peripheral regulatory CD4+ T cells that prevent diabetes onset in nonobese diabetic mice. J Immunol 164 (2000) 240-7.
[37] S. Read, V. Malmstrom, and F. Powrie, Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 192 (2000) 295-302.
[38] R. Pacholczyk, P. Kraj, and L. Ignatowicz, Peptide specificity of thymic selection of CD4+CD25+ T cells. J Immunol 168 (2002) 613-20.
[39] A. Suto, H. Nakajima, K. Ikeda, S. Kubo, T. Nakayama, M. Taniguchi, Y. Saito, and I. Iwamoto, CD4(+)CD25(+) T-cell development is regulated by at least 2 distinct mechanisms. Blood 99 (2002) 555-60.
[40] E. Suri-Payer, A.Z. Amar, A.M. Thornton, and E.M. Shevach, CD4+CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells. J Immunol 160 (1998) 1212-8.
[41] V. Viglietta, C. Baecher-Allan, H.L. Weiner, and D.A. Hafler, Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199 (2004) 971-9.
[42] M.A. Kriegel, T. Lohmann, C. Gabler, N. Blank, J.R. Kalden, and H.M. Lorenz, Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J Exp Med 199 (2004) 1285-91.
[43] J.C. Crispin, A. Martinez, and J. Alcocer-Varela, Quantification of regulatory T cells in patients with systemic lupus erythematosus. J Autoimmun 21 (2003) 273-6.
[44] M.F. Liu, C.R. Wang, L.L. Fung, and C.R. Wu, Decreased CD4+CD25+ T cells in peripheral blood of patients with systemic lupus erythematosus. Scand J Immunol 59 (2004) 198-202.
[45] P.S. Ohashi, T-cell signalling and autoimmunity: molecular mechanisms of disease. Nat Rev Immunol 2 (2002) 427-38.
[46] P.H. Krammer, CD95's deadly mission in the immune system. Nature 407 (2000) 789-95.
[47] R.A. Goldsby, Immunology, W.H. Freeman, New York, 2003.
[48] E.T. Andreakos, B.M. Foxwell, F.M. Brennan, R.N. Maini, and M. Feldmann, Cytokines and anti-cytokine biologicals in autoimmunity: present and future. Cytokine Growth Factor Rev 13 (2002) 299-313.
[49] S.J. Szabo, B.M. Sullivan, S.L. Peng, and L.H. Glimcher, Molecular mechanisms regulating Th1 immune responses. Annu Rev Immunol 21 (2003) 713-58.
[50] M. Falcone, and N. Sarvetnick, Cytokines that regulate autoimmune responses. Curr Opin Immunol 11 (1999) 670-6.
[51] H. Cao, R.G. Wolff, M.S. Meltzer, and R.M. Crawford, Differential regulation of class II MHC determinants on macrophages by IFN-gamma and IL-4. J Immunol 143 (1989) 3524-31.
[52] I. Issemann, and S. Green, Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347 (1990) 645-50.
[53] P. Escher, and W. Wahli, Peroxisome proliferator-activated receptors: insight into multiple cellular functions. Mutat Res 448 (2000) 121-38.
[54] M.D. Leibowitz, C. Fievet, N. Hennuyer, J. Peinado-Onsurbe, H. Duez, J. Bergera, C.A. Cullinan, C.P. Sparrow, J. Baffic, G.D. Berger, C. Santini, R.W. Marquis, R.L. Tolman, R.G. Smith, D.E. Moller, and J. Auwerx, Activation of PPARdelta alters lipid metabolism in db/db mice. FEBS Lett 473 (2000) 333-6.
[55] H. Mano, C. Kimura, Y. Fujisawa, T. Kameda, M. Watanabe-Mano, H. Kaneko, T. Kaneda, Y. Hakeda, and M. Kumegawa, Cloning and function of rabbit peroxisome proliferator-activated receptor delta/beta in mature osteoclasts. J Biol Chem 275 (2000) 8126-32.
[56] B. Desvergne, and W. Wahli, Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 20 (1999) 649-88.
[57] T. Lemberger, R. Saladin, M. Vazquez, F. Assimacopoulos, B. Staels, B. Desvergne, W. Wahli, and J. Auwerx, Expression of the peroxisome proliferator-activated receptor alpha gene is stimulated by stress and follows a diurnal rhythm. J Biol Chem 271 (1996) 1764-9.
[58] E.J. Kim, K.S. Park, S.Y. Chung, Y.Y. Sheen, D.C. Moon, Y.S. Song, K.S. Kim, S. Song, Y.P. Yun, M.K. Lee, K.W. Oh, D.Y. Yoon, and J.T. Hong, Peroxisome proliferator-activated receptor-gamma activator 15-deoxy-Delta12,14-prostaglandin J2 inhibits neuroblastoma cell growth through induction of apoptosis: association with extracellular signal-regulated kinase signal pathway. J Pharmacol Exp Ther 307 (2003) 505-17.
[59] H. Lapillonne, M. Konopleva, T. Tsao, D. Gold, T. McQueen, R.L. Sutherland, T. Madden, and M. Andreeff, Activation of peroxisome proliferator-activated receptor gamma by a novel synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid induces growth arrest and apoptosis in breast cancer cells. Cancer Res 63 (2003) 5926-39.
[60] R.B. Clark, D. Bishop-Bailey, T. Estrada-Hernandez, T. Hla, L. Puddington, and S.J. Padula, The nuclear receptor PPAR gamma and immunoregulation: PPAR gamma mediates inhibition of helper T cell responses. J Immunol 164 (2000) 1364-71.
[61] N. Marx, B. Kehrle, K. Kohlhammer, M. Grub, W. Koenig, V. Hombach, P. Libby, and J. Plutzky, PPAR activators as antiinflammatory mediators in human T lymphocytes: implications for atherosclerosis and transplantation-associated arteriosclerosis. Circ Res 90 (2002) 703-10.
[62] S. Sethi, O. Ziouzenkova, H. Ni, D.D. Wagner, J. Plutzky, and T.N. Mayadas, Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPAR alpha. Blood 100 (2002) 1340-6.
[63] N. Takahashi, T. Kawada, T. Goto, C.S. Kim, A. Taimatsu, K. Egawa, T. Yamamoto, M. Jisaka, K. Nishimura, K. Yokota, R. Yu, and T. Fushiki, Abietic acid activates peroxisome proliferator-activated receptor-gamma (PPARgamma) in RAW264.7 macrophages and 3T3-L1 adipocytes to regulate gene expression involved in inflammation and lipid metabolism. FEBS Lett 550 (2003) 190-4.
[64] C.W. Chen, Y.H. Chang, C.J. Tsi, and W.W. Lin, Inhibition of IFN-gamma-mediated inducible nitric oxide synthase induction by the peroxisome proliferator-activated receptor gamma agonist, 15-deoxy-delta 12,14-prostaglandin J2, involves inhibition of the upstream Janus kinase/STAT1 signaling pathway. J Immunol 171 (2003) 979-88.
[65] H.H. Schmidt, and U. Walter, NO at work. Cell 78 (1994) 919-25.
[66] T. Fujita, K. Uchida, and N. Maruyama, Purification of senescence marker protein-30 (SMP30) and its androgen-independent decrease with age in the rat liver. Biochim Biophys Acta 1116 (1992) 122-8.
[67] M. Yamaguchi, and T. Yamamoto, Purification of calcium binding substance from soluble fraction of normal rat liver. Chem Pharm Bull (Tokyo) 26 (1978) 1915-8.
[68] T. Fujita, J.L. Mandel, T. Shirasawa, O. Hino, T. Shirai, and N. Maruyama, Isolation of cDNA clone encoding human homologue of senescence marker protein-30 (SMP30) and its location on the X chromosome. Biochim Biophys Acta 1263 (1995) 249-52.
[69] T. Fujita, Senescence marker protein-30 (SMP30): structure and biological function. Biochem Biophys Res Commun 254 (1999) 1-4.
[70] Y. Morooka, and M. Yamaguchi, Inhibitory effect of regucalcin on protein phosphatase activity in the nuclei of rat kidney cortex. J Cell Biochem 83 (2001) 111-20.
[71] J. Yamaguchi, K.F. Kusano, O. Masuo, A. Kawamoto, M. Silver, S. Murasawa, M. Bosch-Marce, H. Masuda, D.W. Losordo, J.M. Isner, and T. Asahara, Stromal cell-derived factor-1 effects on ex vivo expanded endothelial progenitor cell recruitment for ischemic neovascularization. Circulation 107 (2003) 1322-8.
[72] N. Suzuki, T. Harada, Y. Mizushima, and T. Sakane, Possible pathogenic role of cationic anti-DNA autoantibodies in the development of nephritis in patients with systemic lupus erythematosus. J Immunol 151 (1993) 1128-36.
[73] J.S. Cameron, Lupus nephritis. J Am Soc Nephrol 10 (1999) 413-24.
[74] J.R. Sedor, M. Konieczkowski, S. Huang, J.H. Gronich, Y. Nakazato, G. Gordon, and C.H. King, Cytokines, mesangial cell activation and glomerular injury. Kidney Int Suppl 39 (1993) S65-70.
[75] M. Adachi, R. Watanabe-Fukunaga, and S. Nagata, Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice. Proc Natl Acad Sci U S A 90 (1993) 1756-60.
[76] J.L. Chu, J. Drappa, A. Parnassa, and K.B. Elkon, The defect in Fas mRNA expression in MRL/lpr mice is associated with insertion of the retrotransposon, ETn. J Exp Med 178 (1993) 723-30.
[77] J.H. Russell, and T.J. Ley, Lymphocyte-mediated cytotoxicity. Annu Rev Immunol 20 (2002) 323-70.
[78] N. Van Houten, and R.C. Budd, Accelerated programmed cell death of MRL-lpr/lpr T lymphocytes. J Immunol 149 (1992) 2513-7.
[79] J.E. Castro, J.A. Listman, B.A. Jacobson, Y. Wang, P.A. Lopez, S. Ju, P.W. Finn, and D.L. Perkins, Fas modulation of apoptosis during negative selection of thymocytes. Immunity 5 (1996) 617-27.
[80] S. Nagata, Human autoimmune lymphoproliferative syndrome, a defect in the apoptosis-inducing Fas receptor: a lesson from the mouse model. J Hum Genet 43 (1998) 2-8.
[81] P.L. Cohen, and R.A. Eisenberg, Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol 9 (1991) 243-69.
[82] 劉秉昭,張琦,路志正, 路志正教授運用經方治療紅斑狼瘡的經驗. 中國中醫藥資訊雜誌 11 (2001) 72.
[83] 路志正,焦樹德, 實用中醫風濕病學, 人民衛生出版社, 北京, 1996.
[84] 陳啟斌,林進財,張恒鴻,吳文祥,陳正傑, 知識發掘法應用於B-code證型類別之決定-以紅斑性狼瘡患者為例. 資訊管理學報 12 (2005) 31-53.
[85] 鐘嘉熙,吳智兵, 陰虛化熱對系統性紅斑狼瘡發病機制研究的啟示. 中國中醫基礎醫學雜誌 6 (1999) 30-33.
[86] 張兆云,范瑞景, 中醫藥防治紅班性狼瘡信息分析與思考. 中國中醫信息雜誌 2 (1995) 29-31.
[87] 艾儒棣, 謹守病機,分期辨證治療紅斑性狼瘡的體會. 四川中醫 9 (1994) 4-5.
[88] 江紅兵, 濕熱病篇運用陰藥規律初探. 四川中醫 19 (2001) 2-3.
[89] 吳玉豐, 龍膽瀉肝湯臨症應用淺析. 中醫藥學刊 22 (2004) 718.
[90] 季衛鋒,厲駒,武中慶,童培建, 龍膽瀉肝湯治療濕熱瘀阻型類風濕關節炎療效觀察. 中醫正骨 11 (2004) 78-79.
[91] 李繼榮, 龍膽瀉肝湯治療濕熱型銀屑病50例. 時珍國醫國藥 9 (2001) 791.
[92] 梁冬梅, 龍膽瀉肝湯治療常見皮膚病. 湖北中醫雜誌 6 (2005) 44.
[93] 張年順, 龍膽瀉肝湯臨床應用規律探討. 山東中醫藥大學學報 5 (1997) 395-397.
[94] 謝鳴, 中醫方劑現代研究, 學苑出版社, 北京, 1997.
[95] 武梅芳,楚立,張建平, 龍膽瀉肝湯的藥理及毒理學實驗研究. 河北中醫藥學報 1 (1996) 1.
[96] 馮亦穎,劉炳治,王巨存, 龍膽瀉肝湯對氧自由基和由羥自由基誘導的脂質過氧化的影響. 中國中醫眼科雜誌 2 (2000) 63-65.
[97] 吳賀算,高玉軍,李秋華, 龍膽瀉肝湯的免疫作用. 中成藥 2 (1984) 21-22.
[98] 行政院衛生署中華藥典中藥集編修小組, 中華中藥典, 行政院衛生署, 台北, 2004.
[99] 張學武,崔長旭,李蓮花, 龍膽草水提物對大鼠肝損傷的保護作用. 四川中醫 5 (2005) 18.
[100] 崔長旭,柳明洙,李天洙,張學武, 龍膽草水提物對d-半乳糖中毒大鼠急性肝損傷的保護作用. 山東中醫雜誌 1 (2006) 20-22.
[101] 那莎,郭國田,王宗殿,龍子江, 梔子及其有效成分藥理研究進展. 中國中醫藥資訊雜誌 1 (2005) 90-92.
[102] 張陸勇, 梔子西紅花總苷對神經心血管及呼吸系統的影響. 中國藥科大學學報 31 (2005) 455-457.
[103] 程合理,趙新民, 梔子苷的抗炎作用實驗研究. 安徽醫藥 8 (2004) 1.
[104] 馬燕,胡強,趙維中, 梔子總苷對小鼠實驗性胃粘膜損傷的保護作用. 時珍國醫國藥 5 (2005) 386.
[105] 張德權,呂飛傑,台建祥,趙世萍,付桂香,付勤, 梔子黃色素對四氯化碳肝損傷小鼠的影響. 營養學報 3 (2002) 269-274.
[106] 王豔蕾,賈玉傑,王選深,薑妙娜,趙景霞, 梔子提取液治療大鼠重症急性胰腺炎的實驗研究. 中國中西醫結合外科雜誌 2 (2003) 119-121.
[107] H.J. Koo, Y.S. Song, H.J. Kim, Y.H. Lee, S.M. Hong, S.J. Kim, B.C. Kim, C. Jin, C.J. Lim, and E.H. Park, Antiinflammatory effects of genipin, an active principle of gardenia. Eur J Pharmacol 495 (2004) 201-8.
[108] Y.C. Shen, W.F. Chiou, Y.C. Chou, and C.F. Chen, Mechanisms in mediating the anti-inflammatory effects of baicalin and baicalein in human leukocytes. Eur J Pharmacol 465 (2003) 171-81.
[109] 陳忻,曹勇, 黃芩苷對肝微粒體脂質過氧化的影響. 北京中醫 1 (2005) 45-47.
[110] 陳桂枝,羅德生,鄭紅花,羅麗芳,李映紅,仰光斌, 四氯化碳肝損傷與脂質過氧化時黃芩煎劑的保護作用. 咸寧學院學報 1 (2005) 31.
[111] 葉曉平,宋純清, 柴胡皂苷藥理研究進展. 中草藥 12 (2004) 1434-1436.
[112] 霍務貞,孫嚴彤,朱盛山, 柴胡有效成分提取條件的研究. 廣東藥學 4 (2005) 1-2.
[113] Y.L. Hsu, P.L. Kuo, L.C. Chiang, and C.C. Lin, Involvement of p53, nuclear factor kappaB and Fas/Fas ligand in induction of apoptosis and cell cycle arrest by saikosaponin d in human hepatoma cell lines. Cancer Lett 213 (2004) 213-21.
[114] 尹華,董曉燁, 當歸藥材的質量標準研究. 中華中醫藥學刊 23 (2005) 1500-1503.
[115] 王豔麗,和水祥,羅金燕, 柴胡皂苷抗腫瘤機制研究進展. 中西醫結合學報 1 (2006) 98-100.
[116] 劉琳娜,梅其炳,程建峰, 當歸揮發油的化學成分分析. 中成藥 2 (2005) 204-206.
[117] 楊鐵虹,賈敏,梅其炳, 當歸多糖對細胞免疫功能的增進作用. 細胞與分子免疫學雜誌 21 (2005) 89-91.
[118] 孫紅旭,趙鵬,顏春魯,李滿生, 當歸多糖影響小鼠胸腺細胞凋亡的實驗研究. 甘肅中醫 11 (2005) 41-42.
[119] 謝叢華,周雲峰,彭綱,劉暉,陳紀,夏明童, 當歸對小鼠放射性肺損傷過程中tnf-α水準的影響. 中華放射腫瘤學雜誌 1 (2005) 59-63.
[120] 陳小憶, 澤瀉臨床應用及免疫調節作用的研究進展. 中國中醫藥科技 1 (2005) 63-64.
[121] 尹春萍,吳繼洲, 澤瀉及其活性成分免疫調節作用研究進展. 中草藥 32 (2001) 1133-1134.
[122] 戴岳,杭秉茜,黃朝林,李佩珍, 澤瀉對免疫系統的影響及抗炎作用. 中國中藥雜誌 10 (1991) 622-625.
[123] 孟洋,彭柏源,華志明,李萍, 生地黃化學成份研究. 中藥材 28 (2005) 293-294.
[124] 馬健,樊巧玲,木村正康, 生地黃對“陰虛”模型小鼠腹腔巨噬細胞Ⅰa抗原表達的影響. 中藥藥理與臨床 2 (1998) 22-23.
[125] 邱靜帆,殷穎, 車前子的藥學研究及其應用. 浙江中西醫結合雜誌 12 (2002) 1.
[126] 王素敏,黎燕峰,代洪燕,裴庭梅,王永利, 車前子調整脂代謝及其抗氧化作用. 中國臨床康復 31 (2005) 248-250.
[127] 李建民, 對《本草綱目》補正中木通有毒一文的商榷. 時珍國藥研究 6 (1994) 47.
[128] 李德勳,趙永成,廖仲祥, 關木通與川木通的比較鑒別. 基層中藥雜誌 3 (2000) 26.
[129] 程一帆,苟虹,劉道剛,王兵, 從取消關木通藥用標準看中藥的不良反應. 實用中醫藥雜誌 5 (2005) 302-303.
[130] 行政院衛生署, 行政院衛生署全面禁用含馬兜鈴酸中藥材及其製劑暨後續管理措施, 台北, 2003.
[131] 莫文先, 木通中毒原因分析. 現代中藥研究與實踐 1 (1999) 57.
[132] 王迎春,仲來福, 關木通對腎上腺毒性及其機制. 毒黃學雜誌 19 (2005) 251.
[133] 張繼,姚健,丁蘭,郭守軍,楊永利, 甘草的利用研究進展. 草原與草坪 2 (2000) 12-17.
[134] 王麗榮,董永軍,王三虎,郝永清,石敏,越明娟,王承民,杭柏林, 甘草多糖對小鼠紅蛋白和巨噬細胞的影響. 安徽農業科學 33 (2005) 1649-1659.
[135] 韓軍, 甘草的藥理作用與臨床應用價值. 實用醫藥雜誌 8 (2003) 17.
[136] 王惠敏, 甘草藥理作用及其臨床應用. 天津中醫學院學報 4 (2004) 184-185.
[137] 劉亞軍,陳金和, 甘草酸二胺對大鼠腦缺血再灌致腦神經細胞凋亡的保護作用. 中國藥理學通報 21 (2005) 126-127.
[138] 楊寶山,陳立豔,馬英驥,華蔓茹, 甘草酸苷對小鼠爆發性肝損傷細胞凋亡抑制作用. 世界華人消化雜誌 13 (2005) 325-329.
[139] 吳碧華,楊得本,龍存國,許可,胡長林, 甘草總黃酮的體外抗氧化作用. 中國臨床康復 36 (2004) 8262-8263.
[140] R. Zimmerman, J. Radhakrishnan, A. Valeri, and G. Appel, Advances in the treatment of lupus nephritis. Annu Rev Med 52 (2001) 63-78.
[141] L.Y. Yang, A. Chen, Y.C. Kuo, and C.Y. Lin, Efficacy of a pure compound H1-A extracted from Cordyceps sinensis on autoimmune disease of MRL lpr/lpr mice. J Lab Clin Med 134 (1999) 492-500.
[142] G. Perez de Lema, H. Maier, E. Nieto, V. Vielhauer, B. Luckow, F. Mampaso, and D. Schlondorff, Chemokine expression precedes inflammatory cell infiltration and chemokine receptor and cytokine expression during the initiation of murine lupus nephritis. J Am Soc Nephrol 12 (2001) 1369-82.
[143] R. Watanabe-Fukunaga, C.I. Brannan, N.G. Copeland, N.A. Jenkins, and S. Nagata, Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356 (1992) 314-7.
[144] H.Y. Wu, and N.A. Staines, A deficiency of CD4+CD25+ T cells permits the development of spontaneous lupus-like disease in mice, and can be reversed by induction of mucosal tolerance to histone peptide autoantigen. Lupus 13 (2004) 192-200.
[145] A. De la Torre, E. Debiton, D. Durand, J.M. Chardigny, O. Berdeaux, O. Loreau, C. Barthomeuf, D. Bauchart, and D. Gruffat, Conjugated linoleic acid isomers and their conjugated derivatives inhibit growth of human cancer cell lines. Anticancer Res 25 (2005) 3943-9.
[146] J.J. Haddad, and H.L. Harb,L-gamma-Glutamyl-L-cysteinyl-glycine (glutathione; GSH) and GSH-related enzymes in the regulation of pro- and anti-inflammatory cytokines: a signaling transcriptional scenario for redox(y) immunologic sensor(s)? Mol Immunol 42 (2005) 987-1014.
[147] P.E. Morgan, A.D. Sturgess, and M.J. Davies, Increased levels of serum protein oxidation and correlation with disease activity in systemic lupus erythematosus. Arthritis Rheum 52 (2005) 2069-79.
[148] J.T. Venkatraman, B. Chandrasekar, J.D. Kim, and G. Fernandes, Genotype effects on the antioxidant enzymes activity and mRNA expression in liver and kidney tissues of autoimmune-prone MRL/MpJ-lpr/lpr mice. Biochim Biophys Acta 1213 (1994) 167-75.
[149] V. Pancholi, Multifunctional alpha-enolase: its role in diseases. Cell Mol Life Sci 58 (2001) 902-20.
[150] A. Sabbatini, M.P. Dolcher, B. Marchini, D. Chimenti, S. Moscato, F. Pratesi, S. Bombardieri, and P. Migliorini, Alpha-enolase is a renal-specific antigen associated with kidney involvement in mixed cryoglobulinemia. Clin Exp Rheumatol 15 (1997) 655-8.
[151] P. Migliorini, F. Pratesi, F. Bongiorni, S. Moscato, M. Scavuzzo, and S. Bombardieri, The targets of nephritogenic antibodies in systemic autoimmune disorders. Autoimmun Rev 1 (2002) 168-73.
[152] J. Mattow, I. Demuth, G. Haeselbarth, P.R. Jungblut, and J. Klose, Selenium-binding protein 2, the major hepatic target for acetaminophen, shows sex differences in protein abundance. Electrophoresis 27 (2006) 1683-91.
[153] N.R. Pumford, J.A. Hinson, R.W. Benson, and D.W. Roberts, Immunoblot analysis of protein containing 3-(cystein-S-yl)acetaminophen adducts in serum and subcellular liver fractions from acetaminophen-treated mice. Toxicol Appl Pharmacol 104 (1990) 521-32.
[154] N.T. Le, and D.R. Richardson, The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim Biophys Acta 1603 (2002) 31-46.
[155] F.M. Torti, and S.V. Torti, Regulation of ferritin genes and protein. Blood 99 (2002) 3505-16.
[156] F.M. Megli, and K. Sabatini, EPR studies of phospholipid bilayers after lipoperoxidation. 1. Inner molecular order and fluidity gradient. Chem Phys Lipids 125 (2003) 161-72.
[157] S. Shetty, M. Ganachari, M.C. Liu, A. Azghani, H. Muniyappa, and S. Idell, Regulation of urokinase receptor expression by phosphoglycerate kinase is independent of its catalytic activity. Am J Physiol Lung Cell Mol Physiol 289 (2005) L591-8.
[158] R. Rosa, C. George, M. Fardeau, M.C. Calvin, M. Rapin, and J. Rosa, A new case of phosphoglycerate kinase deficiency: PGK Creteil associated with rhabdomyolysis and lacking hemolytic anemia. Blood 60 (1982) 84-91.
[159] G. Turner, J. Fletcher, J. Elber, Y. Yanagawa, V. Dave, and A. Yoshida, Molecular defect of a phosphoglycerate kinase variant associated with haemolytic anaemia and neurological disorders in a large kindred. Br J Haematol 91 (1995) 60-5.
[160] H.Y. Luan, S.J. Tang, W. Yang, C.Y. Tsai, G.H. Sun, and K.H. Sun, Monoclonal anti-double-stranded DNA antibodies cross-react with phosphoglycerate kinase 1 and inhibit the expression and production of IL-2 in activated Jurkat T cell line. Clin Immunol 120 (2006) 326-34.
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