水光兴;万毅刚;蒋春明;张慧兰;陈萍;王朝俊;姚建;
SHUI Guangxing1,WAN Yigang2,JIANG Chunming2,ZHANG Huilan3,CHEN Ping1,WANG Chaojun1,YAO Jian4(1.Drum Tower Clinical Institute of Combination of Traditional Chinese Medicine and Western Medicine,Nanjing Universityof Traditional Chinese Medicine,Nanjing 210008,China;2.Department of Traditional Chinese Medicine,Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing 210008,China;3.Nanjing University of Traditional Chinese Medicine,Nanjing 210029,China;4.Department of Molecular Si

• 1:南京中医药大学中西医结合鼓楼临床学院
• 2:南京大学医学院附属鼓楼医院
• 3:南京中医药大学
• 4:日本山梨大学大学院医学工学総合研究部分子情報伝達学講座

摘要(Abstract)：

有关雷公藤多苷(multi-glycoside ofTripterygium wilfordii,GTW)临床药效学的研究主要是针对增殖性肾小球肾炎、狼疮性肾炎、类风湿性关节炎、银屑病等免疫相关性疾病。其临床疗效主要表现在改善相应疾病的临床症状,减少蛋白尿和血尿,减轻关节痛和皮肤损害等。GTW及其活性成分雷公藤甲素(triptolide,T4)药理作用包括抗炎、免疫抑制、保护肾组织上皮细胞等,而且,在拮抗器官移植排斥反应、抑制肿瘤生长、拮抗生殖方面也具备有益的作用。
In the trials of multi-glycoside of Tripterygium wilfordii(GTW) in the field of pharmacodynamics,some clinical characteristics and symptoms,such as proteinuria,hematuria,joint pain,and skin damage,could be improved in the patients with various diseases including proliferative glomerulonephritis,lupus nephritis,rheumatoid arthritis,psoriasis and other immune-related diseases.In this review,it has been also reported to discuss the effects of GTW and Triptolide(T4),which is a bioactive component in GTW on anti-inflammatory,immunosuppression,and protection of epithelial cell in kidney.On the other hand,it is possible to have some beneficial effects on organ transplant rejection,tumor growth and anti-fertility.

关键词(KeyWords)： 雷公藤多苷;雷公藤甲素;临床药效;药理机制
multi-glycoside of Tripterygium wilfordii(GTW);triptolide(T4);clinical effect;mechanism of pharmacology

Abstract:

Keywords:

基金项目(Foundation): 南京市科技计划项目(200905006)

作者(Authors): 水光兴;万毅刚;蒋春明;张慧兰;陈萍;王朝俊;姚建;
SHUI Guangxing1,WAN Yigang2,JIANG Chunming2,ZHANG Huilan3,CHEN Ping1,WANG Chaojun1,YAO Jian4(1.Drum Tower Clinical Institute of Combination of Traditional Chinese Medicine and Western Medicine,Nanjing Universityof Traditional Chinese Medicine,Nanjing 210008,China;2.Department of Traditional Chinese Medicine,Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing 210008,China;3.Nanjing University of Traditional Chinese Medicine,Nanjing 210029,China;4.Department of Molecular Si

参考文献(References)：

• [1]Ma J S,Brach AR,Liu QR.Arevision of the genusTripterygium(Celastraceae)[J].Edinburgh J Bot,1999,56:33.
• [2]Ma J,Dey M,Yang H,et al.Anti-inflammatory and immunosup-pressive compounds fromTripterygium wilfordii[J].Phytochem-isty,2007,68:1172.
• [3]Li X Y.Anti-inflammatory and immunosuppressive components ofTripterygium wilfordiiHook.f.[J].Int J Immunother,1993,9:181.
• [4]Tao X,Lipsky P E.The Chinese anti-inflammatory and immu-nosuppressive herbal remedyTripterygium wilfordiiHook.f[J].Rheum Dis Clin N Amer,2000,26:29.
• [5]Brinker A M,Ma J,Lipsky P E,et al.Medicinal chemistry andpharmacology of genusTripterygium(Celastraceae)[J].Phyto-chemisty,2007,68(6):1819.
• [6]黎磊石,张训,陈光水,等.雷公藤治疗肾小球肾炎的临床研究[J].中华内科杂志,1981,20(4):216.
• [7]戎殳,胡伟新,刘志红,等.系膜增殖性肾小球肾炎的新疗法——雷公藤多甙新治疗方案的疗效观察[J].肾脏病与透析肾移植杂志,1998,5(7):409.
• [8]李静.双倍剂量雷公藤多苷在大量蛋白尿型IgA肾病中的疗效观察[J].药物与临床,2007,16(4):59.
• [9]刘正钊,胡伟新,章海涛,等.激素联合雷公藤多苷治疗Ⅴ型狼疮性肾炎的临床疗效[J].肾脏病与透析肾移植杂志,2008,17(6):512.
• [10]金彩云,胡国华,郑碧忠,等.狼疮性肾炎血清IL-18及雷公藤多苷对其影响的研究[J].中国中药杂志,2008,33(9):1075.
• [11]Cibere J,Deng Z,Lin Y,et al.A randomized double blind place-bo controlled trail of topicalTripterygium wilfordiiin rheumatoidarthritis:reanalysis using logistic regression analysis[J].J Rheu-matol,2003,30:465.
• [12]Tao X,Younger J,Fan F Z,et al.Benefit of an extract ofTriptery-gium wilfordiiHook.f.in patients with rheumatoid arthritis[J].Arthritis Rheum,2002,46:1735.
• [13]Ji S M,Wang Q W,Chen J S,et al.Clinical trial ofTripterygiumwilfordiiHook.f.in human kidney transplantation in China[J].Transplant Proc,2006,38:1274.
• [14]张剑宇,彭岚,刘定华,等.雷公藤对重症肌无力外周血T淋巴细胞亚群的影响[J].中国医药导报,2008,6(5):80.
• [15]Wu S X,Guo N R.Clinical observation on effect oftriptolidetab-let in treating patients with psoriasis vulgaris[J].Chin J IntegrMed,2005,11:147.
• [16]黎磊石,刘志红.中国肾脏病学[M].北京:人民军医出版社,2008.
• [17]杨俊伟,陈朝红,刘栋,等.雷公藤内酯醇通过细胞凋亡阻止人T细胞增殖[J].肾脏病与透析肾移植杂志,1997,6(3):205.
• [18]刘冬舟,褚爱春,齐晖,等.雷公藤内酯醇诱导T淋巴细胞凋亡时Fas/FasL的表达[J].实用医学杂志,2008,24(8):1295.
• [19]刘栋,杨俊伟,陈朝红,等.雷公藤内酯醇诱导人淋巴细胞凋亡时作用与细胞周期的关系[J].中国免疫学杂志,1995,15(10):455.
• [20]于艳秋,张海鹏,杜烨玮,等.雷公藤多甙对急性移植物抗宿主病时小鼠T细胞及其亚群的影响[J].中国中西医结合杂志,2002,22(10):770.
• [21]Mclellan A D,Kampgen E.Functions of myeloid and lymphoiddendritic cells[J].Immunol Lett,2000,72:101.
• [22]朱学军,刘志红,刘栋,等.雷公藤内酯醇对人树突状细胞体外发育及免疫学功能的影响[J].肾脏病与透析肾移植杂志,2001,10(3):217.
• [23]王胜军,谢芳艺,季晓辉,等.雷公藤多甙和白细胞介素-10对人树突状细胞表面人类白细胞抗原-DR和CD80表达及白细胞介素-12P40转录和分泌的影响[J].南京医科大学学报,2001,21(1):1.
• [24]朱彩凤,包自阳,朱斌,等.雷公藤内酯醇对IgA肾病大鼠血清IgA异常糖基化的影响J].中国病理生理杂志,2009,25(1):186.
• [25]曾学军,张乃峥.雷藤氯内酯醇对正常人及类风湿关节炎患者周围单个核细胞及滑膜细胞产生免疫球蛋白的影响[J].药学学报,1997,32(3):171.
• [26]万毅刚,孙伟,陈晓艳,等.雷公藤多苷对抗Thy1.1抗体肾炎肾小球内炎症细胞浸润的抑制作用[J].中国中药杂志,2009,34(1):72.
• [27]邹小明,林文,方向东,等.雷公藤内酯醇对小鼠IL-2产生和IL-2受体表达的影响[J].第一军医大学学报,1999,19(6):507.
• [28]于俊生,吴桂艳,卫艳玲,等.益肾饮合雷公藤多苷对系膜增生性肾小球肾炎大鼠TNF-α和IL-6蛋白表达的影响[J].中国中西医结合肾病杂志,2008,9(3):225.
• [29]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[J].安徽中医学院学报,2006,25(1):27.
• [30]Dirsch V M,Kiemer A K,Wagner H,et al.Thetriterpenoidqui-nonemethide pristimerin inhibits induction of inducible nitric ox-ide synthase in murine macrophages[J].Eur J Pharmacol,1997,336:211.
• [31]Tao X,Schulze-Koops H,Ma L,et al.Effects ofTripterygium wil-fordiiHook.f.extracts on induction of cyclooxygenase 2 activityand prostaglandin E2 production[J].Arthritis Rheum,1998,41:130.
• [32]郭万首,马丽,陶学廉,等.雷公藤对类风湿关节炎病人软骨细胞一氧化氮合成、一氧化氮合酶活性及其mRNA表达的体外抑制作用[J].中华医学杂志,2001,81(17):1035.
• [33]代玉桥,金道忠,邓小华,等.雷公藤甲素对LPS诱导的海马炎症过程中COX-2和iNOS表达的影响[J].神经解剖学杂志,2006,22(5):521.
• [34]Hwang B Y,Lee J H,Koo TH,et al.Kaurane diterpenes from Is-odon japonicus inhibit nitric oxide and prostaglandin E2 produc-tion and NF-κB activation in LPS-stimulated macrophageRAW264.7 cells[J].Planta Med,2001,67:406.
• [35]邵雪婷,冯磊,姚航平,等.雷公藤内酯醇抑制滑膜成纤维细胞COX-2和iNOS表达[J].浙江大学学报,2004,33(2):160.
• [36]Wiggins R C.The spectrumof podocytopathies:a unifying viewofglomerular diseases[J].Kidney Int,2007,71:1205.
• [37]秦卫松,刘志红,曾彩虹,等.雷公藤甲素对Heymann肾炎模型足细胞病变的影响[J].肾病与透析肾移植杂志,2007,16(2):101.
• [38]万毅刚,孙伟,汪洋,等.雷公藤多苷对抗Thy1.1抗体肾炎蛋白尿和足细胞裂隙膜相关分子表达的影响[J].中国中西医结合杂志,2006,26(12):1094.
• [39]Zheng C X,Chen Z H,Zeng C H,et al.Triptolideprotects podo-cytes from puromycin aminonucleoside induced injuryin vivoandin vitro[J].Kidney Int,2008,74:596.
• [40]姚根宏,栾建凤,叶东,等.雷公藤甲素对嘌呤霉素所致足细胞凋亡的抑制作用[J].免疫学杂志,2008,24(5):115.
• [41]Chan E W,Cheng S C,Sin F W,et al.Triptolideinduced cytotox-ic effects on human promyelocytic leukemia,Tcell lymphoma andhuman hepatocellular carcinoma cell lines[J].Toxicol Lett,2001,122:81.
• [42]Li H,Liu Z H,Dai C S,et al.Triptolideinhibits proinflammatoryfactor-induced over-expression of classⅡMHC and B7 moleculesin renal tubular epithelial cells[J].Acta Pharmacol Sin,2002,23:775.
• [43]刘志红,戴春笋,李恒,等.雷公藤内酯醇对人近端肾小管上皮细胞单核细胞趋化因子合成的影响[J].肾病与透析肾移植杂志,2000,9(5):431.
• [44]Xu G,Tu W,Jiang D,et al.Tripterygium wilfordiiHook.f.treat-ment for idiopathic refractory nephrotic syndrome in adults:a me-ta-analysis[J].Nephron Clin Pract,2009,111:c223.
• [45]Nakajo A,Khoshnoodi J,Takenaka H,et al.Mizoribine correctsnephrin biogenesis by restoring intracellular energy balance[J].JAm Soc Nephrol,2007,18:2554.