抗痛风性关节炎中药的研究
|
摘要
痛风性关节炎是一种由于人体内尿酸含量异常升高,尿酸盐在关节等部位析出而引发的炎症反应。随着人类生活水平的提高,高尿酸血症及痛风性疾病的发病率呈升高趋势,迫切需要研究和开发药效好、副作用小的抗痛风性关节炎的新药。
本文采用灌胃尿酸(400mg/kg/d建立高尿酸血症的鹌鹑模型；分别用灌胃次黄嘌呤(500mg/kg)+皮下注射尿酸酶抑制剂氧嗪酸钾(400mg/kg)法与皮下注射尿酸(400mg/kg)法建立了小鼠高尿酸血症模型。实验结果表明：本文采用的造模方法可以使动物血尿酸水平显著提高；黄嘌呤氧化酶抑制剂别嘌醇可以显著性降低由尿酸引起的鹤鹑血尿酸升高,对次黄嘌呤+氧嗪酸钾引起的小鼠血尿酸升高也有明显的抑制作用,但对皮下注射尿酸引起的小鼠血尿酸升高没有明显作用；促尿酸排泄药苯溴马隆可以显著性降低上述三种模型动物的血尿酸水平。
本文对HPLC测定血尿酸含量进行了方法学考察,建立了准确、稳定、可靠的血尿酸测定方法。
本文采用关节腔内注射尿酸钠结晶的方法诱导大鼠产生痛风性关节炎症状。与空白对照组动物相比,模型组动物4h时即可检测到显著肿胀,11h时达到峰值。之后肿胀现象开始逐渐消退,整个过程可持续30h以上。
本文用鹌鹑高尿酸血症模型评价了中药TCM-1的降血尿酸作用。TCM-180%乙醇(V/V)提取物可以显著性降低高尿酸血症鹌鹑的血尿酸浓度,而其水提物的降血尿酸作用不明显。
本文分别研究了穿山龙提取物对用次黄嘌呤+氧嗪酸钾法和注射尿酸法诱导产生的两种小鼠高尿酸血症模型的作用。结果表明穿山龙提取物对两种小鼠高尿酸血症模型均有降血尿酸作用。
本文研究了黄酮类化合物落新妇苷对尿酸钠所致大鼠痛风性关节炎的作用,并探讨了可能的作用机理。研究结果显示：落新妇苷对尿酸盐引起的大鼠关节肿胀具有显著的抑制效果,而秋水仙碱对关节肿胀的抑制作用并不明显；落新妇苷和秋水仙碱均可以显著促进大鼠炎症部位抗炎因子IL-4的表达；落新妇苷还可以促进Th0细胞向Th2细胞分化,提示落新妇苷对尿酸盐引起的大鼠关节肿胀的抑制作用可能是通过抑制在炎症发展过程中具有增强血管通透性作用的Th1型细胞因子的表达而实现。
Gouty arthritis is a kind of inflammation caused by deposits of monosodium urate acid (MSU) in the synovia of joint due to continual elevation of serum urate acid in human body. Owning to improvement of human living standard, prevalence of high purine diet leads to a rise of incidence of hyperuricemia and gout in those years, making it an urgent need for drugs that is more excellent in treating gouty arthristis with less adverse effects.
In this research, quails were administratered with urate acid suspension (400mg/kg) to induce continual elevation of SUA; Hyperuricemia of mouse was induced by subcutaneous injection of urate acid (400mg/kg), or by gavage of hypoxanthine (500mg/kg) in coordination with subcutaneous injection of uricase inhibtor, i.e. potassium oxonate (400mg/kg). Allopurinol, a xanthine oxidase inhibitor, was found to be able to antagonize both the quails'SUA elevation induced with urate acid and the mouse hypreuricemia induced with hypoxanthine and potassium oxonate, but it was inactive to hyperuricemic mouse induced with urate acid. Benzbromarone, another commenly used drug promoting excretion of uric acid, significantly reduced SUA levels of all the animal models in this research.
We established the accurate, robust and reliable method to detect the authentic concentration of serum uric acid with HPLC.
Gouty arthritis was induced by injection of MSU into joint of rat' s ankles. Compared with animals injected with saline, animal ankles injected with MSU can be detected swell since time 4h since artificial damage, Volume of the MSU treated ankles reach a peak at 11h, then decrease slowly in the following hours. The process may last for more than 30 hours.
Hyperuricemic quails were used to assess TCM-1's potential to decrease SUA concentration of the experimental animals.80% ethanol (V/V) extracts of TCM-1 can significantly reduced SUA concentrations of quails induced with uric acid.
Dioscoreae Nipponicae Makino's extracts were found to be able to decrease the level of SUA in hyperuricemia mice induced either by injection of uric acid or by coadministration of hypoxthine and potassium oxonate.
Astilbin was found to be able to inhibit swell at rat's ankle due to MSU-induced inflammation, and promote expression of IL-4 in inflammatory joints and differertiation of T helper cells from ThO phase to Th2 phase. Its inhibitory function to swell of inflammatory joints may owe to its ability to down regulate Thl-type cytokines that are pivotal to increase vascular permeability.
本文采用灌胃尿酸(400mg/kg/d建立高尿酸血症的鹌鹑模型；分别用灌胃次黄嘌呤(500mg/kg)+皮下注射尿酸酶抑制剂氧嗪酸钾(400mg/kg)法与皮下注射尿酸(400mg/kg)法建立了小鼠高尿酸血症模型。实验结果表明：本文采用的造模方法可以使动物血尿酸水平显著提高；黄嘌呤氧化酶抑制剂别嘌醇可以显著性降低由尿酸引起的鹤鹑血尿酸升高,对次黄嘌呤+氧嗪酸钾引起的小鼠血尿酸升高也有明显的抑制作用,但对皮下注射尿酸引起的小鼠血尿酸升高没有明显作用；促尿酸排泄药苯溴马隆可以显著性降低上述三种模型动物的血尿酸水平。
本文对HPLC测定血尿酸含量进行了方法学考察,建立了准确、稳定、可靠的血尿酸测定方法。
本文采用关节腔内注射尿酸钠结晶的方法诱导大鼠产生痛风性关节炎症状。与空白对照组动物相比,模型组动物4h时即可检测到显著肿胀,11h时达到峰值。之后肿胀现象开始逐渐消退,整个过程可持续30h以上。
本文用鹌鹑高尿酸血症模型评价了中药TCM-1的降血尿酸作用。TCM-180%乙醇(V/V)提取物可以显著性降低高尿酸血症鹌鹑的血尿酸浓度,而其水提物的降血尿酸作用不明显。
本文分别研究了穿山龙提取物对用次黄嘌呤+氧嗪酸钾法和注射尿酸法诱导产生的两种小鼠高尿酸血症模型的作用。结果表明穿山龙提取物对两种小鼠高尿酸血症模型均有降血尿酸作用。
本文研究了黄酮类化合物落新妇苷对尿酸钠所致大鼠痛风性关节炎的作用,并探讨了可能的作用机理。研究结果显示：落新妇苷对尿酸盐引起的大鼠关节肿胀具有显著的抑制效果,而秋水仙碱对关节肿胀的抑制作用并不明显；落新妇苷和秋水仙碱均可以显著促进大鼠炎症部位抗炎因子IL-4的表达；落新妇苷还可以促进Th0细胞向Th2细胞分化,提示落新妇苷对尿酸盐引起的大鼠关节肿胀的抑制作用可能是通过抑制在炎症发展过程中具有增强血管通透性作用的Th1型细胞因子的表达而实现。
Gouty arthritis is a kind of inflammation caused by deposits of monosodium urate acid (MSU) in the synovia of joint due to continual elevation of serum urate acid in human body. Owning to improvement of human living standard, prevalence of high purine diet leads to a rise of incidence of hyperuricemia and gout in those years, making it an urgent need for drugs that is more excellent in treating gouty arthristis with less adverse effects.
In this research, quails were administratered with urate acid suspension (400mg/kg) to induce continual elevation of SUA; Hyperuricemia of mouse was induced by subcutaneous injection of urate acid (400mg/kg), or by gavage of hypoxanthine (500mg/kg) in coordination with subcutaneous injection of uricase inhibtor, i.e. potassium oxonate (400mg/kg). Allopurinol, a xanthine oxidase inhibitor, was found to be able to antagonize both the quails'SUA elevation induced with urate acid and the mouse hypreuricemia induced with hypoxanthine and potassium oxonate, but it was inactive to hyperuricemic mouse induced with urate acid. Benzbromarone, another commenly used drug promoting excretion of uric acid, significantly reduced SUA levels of all the animal models in this research.
We established the accurate, robust and reliable method to detect the authentic concentration of serum uric acid with HPLC.
Gouty arthritis was induced by injection of MSU into joint of rat' s ankles. Compared with animals injected with saline, animal ankles injected with MSU can be detected swell since time 4h since artificial damage, Volume of the MSU treated ankles reach a peak at 11h, then decrease slowly in the following hours. The process may last for more than 30 hours.
Hyperuricemic quails were used to assess TCM-1's potential to decrease SUA concentration of the experimental animals.80% ethanol (V/V) extracts of TCM-1 can significantly reduced SUA concentrations of quails induced with uric acid.
Dioscoreae Nipponicae Makino's extracts were found to be able to decrease the level of SUA in hyperuricemia mice induced either by injection of uric acid or by coadministration of hypoxthine and potassium oxonate.
Astilbin was found to be able to inhibit swell at rat's ankle due to MSU-induced inflammation, and promote expression of IL-4 in inflammatory joints and differertiation of T helper cells from ThO phase to Th2 phase. Its inhibitory function to swell of inflammatory joints may owe to its ability to down regulate Thl-type cytokines that are pivotal to increase vascular permeability.
引文
[1]Amy C. Cannella, Ted R. Mikuls. Understanding Treatments for Gout[J]. The American Journal of managed care,2005,11(sup15):s451-s458.
[2]Arthur L. Weaver. Epidemiology of gout[J]. Cleveland Clinic Journal of Medicine, 2008,75(Supp15):S9-S12.
[3]L. Annemans, E Spaepen, M Gaskin, et al. Gout in the UK and Germany:prevalence, comorbidities, and management in general practice 2000-2005[J]. Ann Rheum Dis, 2008,67:960-966.
[4]Raquel Villegas, Yong bing Xiang, Qiu yin Cai, et al. Prevalence and Determinants of Hyperuricemia in Middle-Aged, Urban Chinese Men[J]. Metabolic Syndrome and Related Disorders,2010,8(3):263-270.
[5]Shih Wei Lai, Chiu Shong Liu, Tsann Lin, et al. prevalence of gout and hyperuricemia in Taiwan:A Hospital-Based, Cross-Sectional Study[J]. Southern Medical Journal,2009,102(7):772-773.
[6]Hairong Nan, Qing Qiao, Yanhu Dong, et al. The prevalence of hyperuricemia in a population of the coastal city of Qingdao, China[J]. The Journal of Rheumatology, 2006,33(7):1346-1350.
[7]Gim Gee Teng, Raj Nair, Kenneth G. Saag. Pathophysiology, Clinical Presentation and Treatment of Gout[J]. Drugs,2006,66(12):1547-1563.
[8]Fernando Perez Ruiz, Nicola Dalbeth, Naomi Schlesinger. Febuxostat, A novel drug for the treatment of hyperuricemia of gout[J]. Future Rheumatol, 2008,3(5):421-427.
[9]H. R. Schumacher Jr, M. A. Becker, E. Lloyd, et al. Febuxostat in the treatment of gout:5-yr findings of the Focus efficacy and safety study[J]. Rheumatology, 2009,48:188-194.
[10]Naomi Schlesinger. Overview of the Management of Acute Gout and the Role of Adrenocorticotropic Hormone[J]. Drugs,2008,68 (4):407-415.
[11]王淳,高学敏,张建军.痹病辨证与辨病选药思路探讨[J].中华中医药杂志,2008,23(7)：602-606.
[12]Mai Thanh Thi Nguyen, Suresh Awale, Yasuhiro Tezuka, et al. Hypouricemic Effects of Acacetin and 4,5-O-Dicaffeoylquinic Acid Methyl Ester on Serum Uric Acid Levels in Potassium Oxonate-Pretreated Rats[J]. Biol. Pharm. Bull, 2005,28(12):2231-2234.
[13]Shifu Mo, Feng Zhou, Yaozhong Lv, et al. Hypouricemic Action of Selected Flavonoids in Mice:Structure-Activity Relationships[J]. Biol. Pharm. Bull, 2007,30(8):1551-1556.
[14]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.
[15]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.
[16]Xiangwei Wu, Maki Wakamiya, Sukeshi Vaishnav, et al. Hyperuricemia and urate nephropathy in urate oxidasedeficient mice[J]. Proc. Natl. Acad. Sci. USA, 1994,1 (91):742-746.
[17]Patricia A. Wright. Nitrogen Excretion:Three end products, Many Physiological roles[J]. The Journal of Experimental Biology,1995,198:273-281.
[18]刘小青,张冰,刘春梅,等.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.
[19]J. S. Faires, D. J. Mccarty. Acute arthritis in man and dog after intrasynovial injection of sodium urate crystals [J]. The Lancet,1962,280(7258):682.
[20]Carmelinda Ruggiero, Antonio Cherubini, Alessandro Ble, et al. Uric acid and inflammatory markers [J]. European Heart Journal,2006,27:1174-1181.
[21]William John Martin, Michaela Walton, Jacquie Harper. Resident Macrophages Initiating and Driving Inflammation in a Monosodium Urate Monohydrate Crystal-Induced Murine Peritoneal Model of Acute Gout [J]. Arthritis & Rheumatism,2009,60(1):281-289.
[22]Charles J. Roberge, Rinalda de MCdicis, Jean Michel Dayer, et al. Crystal-induced neutrophil activation. V. Differential production of biologically active IL-1 and IL-1 receptor antagonist [J]. The Journal of Immunology, 1994,152(11):5485-5494.
[23]Philippe Desaulniers, Maria Fernandes, Caroline Gilbert, et al. Crystal-induced neutrophil activation. Ⅶ. Involvement of Syk in the responses to monosodium urate crystals [J]. Journal of Leukocyte Biology,2001,70(4):659-668.
[24]C. Schiltz, F. Liote, F. Prudhommeaux, et al. Monosodium Urate Monohydrate Crystal-Induced Inflammation In Vivo[J]. Arthritis & Rheumatism,2002,46(6): 1643-1650.
[25]Carle Ryckman, Shaun R. McColl, Karen Vandal, et al. Role of S100A8 and S100A9 in Neutrophil Recruitment in Response to Monosodium Urate Monohydrate Crystals in the Air-Pouch Model of Acute Gouty Arthritis[J]. Arthritis & Rheumatism,2003,48(8):2310-2320.
[26]D R Blake, N D Hall, P A Bacon, et al. Effect of a specific iron chelating agent on animal models of inflammation [J]. Ann Rheum Dis,1983,42:89-93.
[27]Pandey S. Various techniques for the evaluation of anti arthritic activity in animal models[J]. J Adv Pharm Tech Res,2010,1:164-71.
[28]Evan Prince Sabina, Shruthi Nagar, Mahaboobkhan Rasool. A Role of Piperine on Monosodium Urate Crystal-Induced Inflammation-An Experimental Model of Gouty Arthritis[J]. Inflammation,2011,34(3):184-192.
[29]Charles W. Denko, Mark Petricevic. Sympathetic or reflex footpad swelling due to crystal-induced inflammation in the opposite foot[J]. Inflammation, 1978,3(1):81-86.
[30]U. A. S. Al Khalidi, T. H. Chaglassian. The species distribution of xanthine oxidase[J]. Biochem J,1965,97(1):318-320.
[31]Jingqun Huang, Siwang Wang, Miaozhang Zhu, et al. Effects of Genistein, Apigenin, Quercetin, Rutin and Astilbin on serum uric acid levels and xanthine oxidase activities in normal and hyperuricemic mice[J]. Food and Chemical Toxicology,2011,9(49):1943-1947.
[32]James J. Carroll, Holly Coburn, Roberta Douglass, et al. A Simplified Alkaline Phosphotungstate Assay for Uric Acid in Serum[J]. Clinical Chemistry, 1971,17(3):158-160.
[33]Jyh-Myng Zen, Jia-Jen Jou, Govindasamy Ilangovan. Selective voltammetric method for uric acid detection using pre-anodized Nafion-coated glassy carbon electrodes[J]. Analyst,1998,123:1345-1350.
[34]Su-Hua Huang, Yu-Chuan Shih, Chung-Yu Wu, et al. Detection of serum uricacid using the optical polymeric enzyme biochip system[J]. Biosensors and Bioelectronics,2004,19(12):1627-1633.
[35]S.K. George, M.T. Dipu, U.R. Mehra, et al. Improved HPLC method for the simultaneous determination of allantoin, uricacid and creatinine in cattle urine[J]. Journal of Chromatography B,2006,832(1):134-137.
[36]Bernhard Widner, Ernst R. Werner, Harald Schennach, et al. Simultaneous Measurement of Serum Tryptophan and Kynurenine by HPLC[J]. Clinical Chemistry,1997,43(12):2424-2426.
[37]郁颖佳,郑晓伟,黄滔敏,等.高效液相色谱法测定人体血浆中尿酸的浓度[J].复旦学报(医学版),2006,33(2)：273-275.
[38]D. W. Warnock, M. D. Richardson, A. Turner. High performance liquid chromatographic (HPLC) and other non-biological methods for quantitation of antifungal drugs[J]. Journal of Antimicrobial Chemotherapy,1982,10:467-478.
[39]刘二刚,傅旭春,钱莺,等.柱前衍生HPLC法测定大鼠肾组织中羟脯氨酸的含量[J].浙江大学学报(医学版),2012,41(2)：188-191.
[40]E. Cendejas-Bueno, A. Forastiero, J. L. Rodriguez-Tudela, et al. HPLC/UV or bioassay:two valid methods for posaconazole quantification in human serum samples[J]. Clinical Microbiology and Infection,2011:1-7.
[41]H. Ralph Schumacher. The pathogenesis of gout[J]. Cleveland Clinic Journal of Medicine,2008,75(sup15):S2-S4.
[42]Jiyuan Zhao, Qionglin Liang, Guoan Luo, et al. Purine Metabolites in Gout and Asymptomatic Hyperuricemia:Analysis by HPLC-Electrospray Tandem Mass Spectrometry[J]. Clinical Chemistry,2005,51(9):1742-1744.
[43]Juan G. Puig, Fel i citas A. Mateos, Manuel L. Jim e nez, et al. Renal excretion of hypoxanthine and xanthine in primary gout[J]. The American Journal of Medicine, 1988,85(4):533-537.
[44]William R. Wilcox, Ali Khalaf. Solubility of uric acid and monosodium urate[J]. Med. & Biol. Eng,1972,10:522-531.
[45]Fires J. S., Mccarty D. J., Jr. Acute synovitis in normal joints of man and dog produced by injections of microcrystalline sodium urate, calcium oxalate and corticosteroid esters[J]. Arthritis & rheumatism,1962(5):295.
[46]Paulding Phelps, Daniel J. McCarty. Crystal-Induced Inflammation in Canine Joints Ⅱ. Importance of Polymorphonuclear Leukocytes[J]. JEM, 1966,124(1):115-126.
[47]Darshna R. Yagnik, Betsy J. Evans, Oliver Florey, et al. Macrophage Release of Transforming Growth Factor β 1During Resolution of Monosodium Urate Monohydrate Crystal-Induced Inflammation[J]. Arthritis & Rheumatism, 2004,50(7):2273-2280.
[48]P. T. Chapman, F. Jamar, A. A. Harrison, et al. Characterization of E-selectin expression, leucocyte traffic and clinical sequelae in urate crystal-induced inflammation:An insight into gout[J]. British Journal of Rheumatology, 1996,35:323-334.
[49]Joel R. Pittman, Michael H. Bross. Diagnosis and management of gout[J]. American family physician,1999,59(7):1799-1806.
[50]国家药典委员会.中华人民共和国药典(一部)[M].北京：化学工业出版社,2010：250-251.
[51]楼芳嫣.中药穿地龙的研究进展[J].中国药师,2010,7(13)：1041-1043.
[52]高菁,李靖,于秀辰.商宪敏教授论治痛风经验[J].北京中医药大学学报(中医临床版),2005,12(3)：30-31.
[53]张伟锋,刘宝山.薯蓣皂苷的药理作用研究进展[J].世界中西医结合杂志,2010,5(6)：543-545.
[54]Bonifacio A'lvarez Lario, Jesu's Macarron Vicente. Uric acid and evolution[J]. Rheumatology,2010,49:2010-2015.
[55]Yan Shi, Ashley D. Mucsi, Gilbert Ng. Monosodium urate crystals ininflammation and immunity[J]. Immunological Reviews,2010(233):203-217.
[56]Fabio Martinon, Laurie H. Glimcher. Gout:new insights into an old disease[J]. The Journal of Clinical Investigation,2006,116(8):2073-2075.
[57]Sanjeev Mariathasan, Denise M. Monack. Inflammasome adaptors and sensors:intracellular regulators of infection and inflammation[J]. Immunology, 2007,1(7):31-40.
[58]R Terkeltaub, J S Sundy, H R Schumacher, et al. The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis:results of a placebocontrolled, monosequence crossover, nonrandomised, single-blind pilot study [J]. Ann Rheum Dis,2009,68:1613-1617.
[59]Charles A. Dinarello. Anti-inflammatory Agents:Present and Future[J]. Cell, 2010,140:935-950.
[60]M. Miyata, H. Ohira, S. Suzuk, et al. Significance of low mRNA level of interleukin-4 and-10 in mononuclear cell of the synovial fluid of patients with rheumatoid arthritis[J]. Clin Rheumatol,2000,19:365-370.
[61]F. M. Cicuttini, K. A. Byron, D. Maher, et al. Serum IL-4, IL-10 and IL-6 in inflammatory arthritis [J]. Rheumatol Int,1995,14:201-206.
[62]Yousuke Murakami, Tohru Akahoshi, Shinichi Kawai, et al. Antiinflammatory Effect of Retrovirally Transfected Interleukin-10 on Monosodium Urate Monohydrate Crystal-Induced Acute Inflammation in Murine Air Pouches[J]. Arthritis & Rheumatism,2002,46(9):2504-2513.
[63]James M. Woods, Kenneth J. Katschke, Jr., et al. IL-4 Adenoviral Gene Therapy Reduces Inflammation, Proinflammatory Cytokines, Vascularization, and Bony Destruction in Rat Adjuvant-Induced Arthritis[J]. J Immunol, 2001,166:1214-1222.
[64]Fietta P, Delsante G. The effector T helper cell triade. Rivista di biologia[J]. Jan-Apr,2009,102(1):61-74.
[65]Shu Lin Chang, Yi Ming Chiang, Cicero Lee Tian Chang, et al. Flavonoids, centaurein and centaureidin, from Bidens pilosa, stimulate IFN- Y expression [J]. Journal of Ethnopharmacology,2007,112:232-236.
[66]Xu Qiang, Sun Yang. Novel Immunosuppression Stemming from the Selective Activity of Chinese Herbal Grugs[J]. Progress in Chemistry,2009,21(1):55-62.
[67]宋少华,沈筱云,丁国善,等.落新妇苷对小鼠骨髓来源树突状细胞成熟及免疫功能的抑制作用[J].中西医结合学报,2010,8(2)：145-151.
[68]陈涛,潘铁成,高思海,等.落新妇甙对小鼠心脏移植排斥反应的抑制作用[J].山东医药,2006,46(33)：7-8.
[69]Mingjian Fei, Xuefeng Wu, Qiang Xu. Astilbin inhibits contact hypersensitivity through negative cytokine regulation distinct from cyclosporin A[J]. Journal of Allergy and Clinical Immunology,2005,116(6):1350-1356.
[70]Hong wei Yi, Xiao min Lu, Feng Fang, et al. Astilbin inhibits the adhesion of T lymphocytes via decreasing TNF-αand its associated MMP-9 activity and CD44 expression[J]. International Immunopharmacology,2008:1467-1474.
[71]Yu Cai, Ting Chen, Qiang Xu. Astilbin suppresses delayed-type hypersensitivity by inhibiting lymphocyte migration[J]. Journal of Pharmacy and Pharmacology, 2003,55(5):691-696.
[72]Y. Cai, T. Chen, Q. Xu. Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes[J]. Inflamm. Res,2003,(52):334-340.
[73]赵金平,李平,张韵凤,等.转化生长因子β 1对心脏移植排斥反应中细胞黏附分子表达的影响[J].华中科技大学学报(医学版),2009,29(2)：212-214.
[74]林慧庆,王建军,唐建,等.落新妇甙对大鼠肺移植排斥反应的抑制作用[J].微循环学杂志,2008,18(2)：8-9.
[75]高思海,李平,陈涛,等.落新妇甙对心脏移植排斥反应中细胞因子表达的影响[J].中华小儿外科杂志,2006,(2)：87-89.
[76]J. D. L. Wilhelm. Mechanisms responsible for increased vascular permeability in acute inflammation[J]. Inflammation Research,1973,3(5):297-306.
[77]D. L. Wilhelm, Brenda Mason. Vascular permeability changes in inflammation: The role of endogenous permeability factors in mild thermal injury[J]. Br J Exp Pathol,1960,41 (5):487-506.
[78]G. Logan, D. L. Wilhelm. Vascular permeability changes in inflammation:Ⅱ. The effect of lecithinase antagonists in ultraviolet injury in the guinea-pig[J]. Br J Exp Pathol,1966,47(4):324-330.
[79]Robert Paul, Uwe Koedel, Frank Winkler, er al. Lack of IL-6 augments inflammatory responses but decreases permeability in bacterial meningitis[J]. Brain,2003,126:1873-1882
[80]Sumagin R, Lomakina E, Sarelius I H. Leukocyte-endothlial cell interactions are linked to vascular permeability via ICAM-1-mediated signaling[J]. Am J. Phsiol Heart Circ Physiol,2008,19:H969-H977.
[81]N. A. Klimenko, E. A. Pavlova. Role of leukocytes in increased vascular permeability in inflammation[J]. Bluletin of experimental biology and medicine, 1998,128(2):800-802.
[82]Pascale Chomarat, Edouard Vannier, Julie Dechanet, et al. Balance of IL-1 Receptor Antagonist/1L-1 β in Rheumatoid Synovium and Its Regulation by IL-4 andIL-10[J]. The Journal of Immunology,1995:1432-1439.
[83]Enver Akalin, Wayne W Hancock, Norberto Perico, et al. Blocking cell microtubule assembly inhibits the alloimmune response in vitro and prolongs renal allograft survival by inhibition of Thl and sparing of Th2 cell function in vivo[J]. Journal of the American Society of Nephrology,1995,5:1418-1425.
[84]Yoshihiko Tanaka, Shinjiro Hamano, Kazuhito Gotoh, et al. T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-a subunit controlled by the Rac activator Dock2[J]. Nature Immunology,2007,8:1067-1075.
[85]Susanne J Szabo, Sean T Kim, Gina L Costa, et al. A Novel Transcription Factor, T-bet, Directs Thl Lineage Commitment[J]. Cell,2000,100:655-669.
[86]Andrew Yatesa, Robin Callarda, Jaroslav Stark. Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiations model for cellular decision-making[J]. Journal of Theoretical Biology,2004,231 (2):181-196.
[87]Ruslan Medzhitov. Inflammation 2010:New Adventures of an Old Flame[J]. Cell, 2010,140:771-776.
[88]John Kanellis, Duk-Hee Kang. Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease [J]. Seminars in Nephrology,2005,25(1):39-42.
[89]Loretta Cain, Anoop Shankar, Alan M. Ducatman, et al. The relationship between serum uric acid and chronic kidney disease among Appalachian adults[J]. Nephrology Dialysis Transplantation,2010,25(11):3593-3599.
[90]Marilda Mazzali, Jeremy Hughes, Yoon-Goo Kim, et al. Elevated Uric Acid Increases Blood Pressure in the Rat by a Novel Crystal-Independent Mechanism[J]. Hypertension,2001,11:1100-1106.
[91]Bryan Emmerson. Hyperlipidaemia in hyperuricaemia and gout[J]. Ann Rheum Dis, 1998,57:509-510.
[92]Hyon K. Choi, David B. Mount, Anthony M. Reginato. Pathogenesis of Gout[J]. Ann Intern Med,2005,143:499-516.
[1]Edward Roddy, Michael Doherty. Epidemiology of gout[J]. Arthritis Research & Therapy,2010,12:223.
[2]Diana Rudan, Ozren Polasek, Ivana Kolcic. Uric Acid:the Past Decade[J]. Croat Med J,2010,51:1-6.
[3]Hak. A Elisabeth, Choi. Hyon K. Lifestyle and gout[J]. Current Opinion in Rheumatology,2008,20(2):179-186.
[4]Hanyao Huang, Lawrence J. Appel, Michael J. Choi, et al. The Effects of Vitamin C Supplementation on Serum Concentrations of Uric Acid[J]. Arthritis & Rheumatism, 2005,52(6):1843-1847.
[5]By T. Gibson, R. Waterworth, P. Hatfield, et al. Hyperuricemia, Gout and Kidney Function in New Zealand Maori Men[J]. British Journal of Rheumatology, 1984,23:276-282.
[6]Matthias A. Hediger, Richard J Johnson, Hiroki Miyazaki, et al. Molecular Physiology of Urate Transport[J]. Physiology,2005,20:125-133.
[7]Choi Hyon K, Zhu Yanyan, Mount. David B. Genetics of gout[J]. Current Opinion in Rheumatology,2010,3.22(2):144-151.
[8]Philip L. Riches, Alan F. Wright, Stuart H. Ralston. Recent insights into the pathogenesis of hyperuricaemia and gout[J]. Human Molecular Genetics, 2009,18(2):R177-R184.
[9]J. T. Scott. Drug-induced gout[J]. Bailliere's Clinical Rheumatology, 1991,5(1):39-60.
[10]Angel Lopez Cuenca, Vanessa Roldan, Francisco Marin. Hypouricemic effect of statins:Another pleiotropic benefit[J]. J Thorac Cardiovase S(?)g, 2010,139:1358-1359.
[11]Perez-Ruiz F, Liote F. Lowering serum uric acid levels:what is the optimal target for improving clinical outcomes in gout[J]. Arthritis Rheum,2007,57:1324-1328.
[12]Leslie R Harrold, Susan E Andrade, Becky A Briesacher, et al. Adherence with urate-lowering therapies for the treatment of gout[J]. Arthritis Research & Therapy, 2009,11:R46.
[13]Lada Beara Lasic, Michael H Pillinger, David S Goldfarb. Advances in the management of gout:Critical appraisal of febuxostat in the control of hyperuricemiaInternational[J]. Journal of Nephrology and Renovascular Disease, 2010:3-10.
[14]M K Reinders, E N van Roon, T L Th A Jansen, et al. Efficacy and tolerability of urate-lowering drugs in gout:A randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol[J]. Ann Rheum Dis,2009,68:51-56.
[15]Lee. Ming Han H, Graham. Garry G, Williams. Kenneth M. A Benefit-Risk Assessment of Benzbromarone in the Treatment of Gout:Was its Withdrawal from the Market in the Best Interest of Patients[J]. Drug Safety,2008,31(8):643-665.
[16]Bruce N Cronstein, Robert Terkeltaub. The inflammatory process of gout and its treatment[J]. Arthritis Research & Therapy,2006,8(Suppl 1):S3-S9.
[17]Gim Gee Teng, Raj Nair, Kenneth G. Saag. Pathophysiology, Clinical Presentation and Treatment of Gout[J]. Drugs,2006,66(12):1547-1563.
[18]Yu, Kuang Hui. Febuxostat:A Novel Non-Purine Selective Inhibitor of Xanthine Oxidase for the Treatment of Hyperuricemia in Gout[J]. Recent Patents on Inflammation & Allergy Drug Discovery,2007,1(1):69-75.
[19]Fernando Perez Ruiz, Nicola Dalbeth, Naomi Schlesinger. Febuxostat, a novel drug for the treatment of hyperuricemia of gout[J]. Future Rheumatol,2008,3(5): 421-427.
[20]Mattheus K Reinders, Tim L Th A Jansen. Management of hyperuricemia in gout:Focus on febuxostat[J]. Clinical Interventions in Aging,2010,5:7-18.
[21]Merry R. Sherman, Mark G. P. Saifer, Fernando Perez-Ruiz. PEG-uricase in the management of treatment-resistant gout and hyperuricemia[J]. Advanced Drug Delivery Reviews,2008,60(1):59-68.
[22]Bruno Vogt. Urate oxidase(rasburicase) for treatment of severe tophaceous gout[J]. Nephrol Dial Transplant,2005,20:431-433.
[23]Michael S. Hershfield, L. Jackson Roberts, Nancy J. Ganson, et al. Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo[J]. PNAS,2010,107(32):14351-14356.
[24]John S. Sundy, Michael A. Becker, Herbert S. B. Baraf, et al. Reduction of Plasma Urate Levels Following Treatment With Multiple Doses of Pegloticase(Polyethylene Glycol-Conjugated Uricase) in Patients With Treatment-Failure Gout Results of a Phase Ⅱ Randomized Study[J]. Arthritis & Rheumatism,2008,58:2882-2891.
[25]Krishnan E, Lienesch D, Kwoh CK. Gout in ambulatory care settings in the United States[J]. J Rheumatol,2008,35:498-501.
[26]Hector Bueno, Alfredo Bardaji, Paola Patrignani, et al. Use of Non-Steroidal Antiinflammatory Drugs and Type-Specific Risk of Acute Coronary Syndrome[J]. The American Journal of Cardiology,2009,12:1-5.
[27]N. Lawrence Edwards, Terence Gibson, Robert A. Terkeltaub. Gout Treatment[J]. A Clinician's Pearls and Myths in Rheumatology,2010:361-367.
[28]Robert Terkeltaub. Novel therapies for treatment of gout and hyperuricemia[J]. Arthritis Research & Therapy,2009,11:236.
[29]Alexander So, Thibaut De Smedt, Sylvie Revaz, et al. A pilot study of IL-1 inhibition by anakinra in acute gout[J]. Arthritis Research & Therapy,2007,9:R28.
[30]R Terkeltaub, J S Sundy, H R Schumacher, et al. The interleukin 1 inhibitor rilonacept in placebo-controlled, monosequence crossover, treatment of chronic gouty arthritis:Results of a non-randomised, single-blind pilot study[J]. Ann Rheum Dis,2009,68:1613-1617.
[31]Vikneswaran Murugaiyah, Kit Lam Chan. Mechanisms of antihyperuricemic effect of Phyllan thus niruri and its lignin constituents [J]. Journal of Ethnopharmacology, 2009,124:233-239.
[32]Zhifeng Yu, Wing Ping Fong, Christopher H. K. Cheng. The Dual Actions of Morin as a Hypouricemic Agent:Uricosuric Effect and Xanthine Oxidase Inhibitory Activity[J]. JPET,2006,316(1):169-175.
[33]Xing Wang, Caiping Wang, Qinghua Hu, et al. The dual actions of Sanmiao wan as a hypouricemic agent:Down-regulation of hepatic XOD and renal mURAT1 in hyperuricemic mice[J]. Journal of Ethnopharmacology,2010,128:107-115.
[34]Zuoqi Ding, Yue Dai, Zhengtao Wang. Hypouricemic Action of Scopoletin Arising from Xanthine Oxidase Inhibition and Uricosuric Activity [J]. Planta Med, 2005,71(2):183-185.
[35]Xiaoyu Liu, Ruohua Chen, Yanjun Shang, et al. Lithospermic acid as a novel xanthine oxidase inhibitor has anti-inflammatory and hypouricemic effects in rats[J]. Chemico-Biological Interactions,2008,176(2-3):137-142.
[36]Jieun Lee, Jeongmi An, Hee-Jin Yang, et al. Reparatory and Preventive Effects of Oriental Herb Extract Mixture(OHEM) on Hyperuricemia and Gout[J]. Food Sci. Biotechnol,2010,19(2):517-524.
[2]Arthur L. Weaver. Epidemiology of gout[J]. Cleveland Clinic Journal of Medicine, 2008,75(Supp15):S9-S12.
[3]L. Annemans, E Spaepen, M Gaskin, et al. Gout in the UK and Germany:prevalence, comorbidities, and management in general practice 2000-2005[J]. Ann Rheum Dis, 2008,67:960-966.
[4]Raquel Villegas, Yong bing Xiang, Qiu yin Cai, et al. Prevalence and Determinants of Hyperuricemia in Middle-Aged, Urban Chinese Men[J]. Metabolic Syndrome and Related Disorders,2010,8(3):263-270.
[5]Shih Wei Lai, Chiu Shong Liu, Tsann Lin, et al. prevalence of gout and hyperuricemia in Taiwan:A Hospital-Based, Cross-Sectional Study[J]. Southern Medical Journal,2009,102(7):772-773.
[6]Hairong Nan, Qing Qiao, Yanhu Dong, et al. The prevalence of hyperuricemia in a population of the coastal city of Qingdao, China[J]. The Journal of Rheumatology, 2006,33(7):1346-1350.
[7]Gim Gee Teng, Raj Nair, Kenneth G. Saag. Pathophysiology, Clinical Presentation and Treatment of Gout[J]. Drugs,2006,66(12):1547-1563.
[8]Fernando Perez Ruiz, Nicola Dalbeth, Naomi Schlesinger. Febuxostat, A novel drug for the treatment of hyperuricemia of gout[J]. Future Rheumatol, 2008,3(5):421-427.
[9]H. R. Schumacher Jr, M. A. Becker, E. Lloyd, et al. Febuxostat in the treatment of gout:5-yr findings of the Focus efficacy and safety study[J]. Rheumatology, 2009,48:188-194.
[10]Naomi Schlesinger. Overview of the Management of Acute Gout and the Role of Adrenocorticotropic Hormone[J]. Drugs,2008,68 (4):407-415.
[11]王淳,高学敏,张建军.痹病辨证与辨病选药思路探讨[J].中华中医药杂志,2008,23(7)：602-606.
[12]Mai Thanh Thi Nguyen, Suresh Awale, Yasuhiro Tezuka, et al. Hypouricemic Effects of Acacetin and 4,5-O-Dicaffeoylquinic Acid Methyl Ester on Serum Uric Acid Levels in Potassium Oxonate-Pretreated Rats[J]. Biol. Pharm. Bull, 2005,28(12):2231-2234.
[13]Shifu Mo, Feng Zhou, Yaozhong Lv, et al. Hypouricemic Action of Selected Flavonoids in Mice:Structure-Activity Relationships[J]. Biol. Pharm. Bull, 2007,30(8):1551-1556.
[14]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.
[15]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.
[16]Xiangwei Wu, Maki Wakamiya, Sukeshi Vaishnav, et al. Hyperuricemia and urate nephropathy in urate oxidasedeficient mice[J]. Proc. Natl. Acad. Sci. USA, 1994,1 (91):742-746.
[17]Patricia A. Wright. Nitrogen Excretion:Three end products, Many Physiological roles[J]. The Journal of Experimental Biology,1995,198:273-281.
[18]刘小青,张冰,刘春梅,等.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.
[19]J. S. Faires, D. J. Mccarty. Acute arthritis in man and dog after intrasynovial injection of sodium urate crystals [J]. The Lancet,1962,280(7258):682.
[20]Carmelinda Ruggiero, Antonio Cherubini, Alessandro Ble, et al. Uric acid and inflammatory markers [J]. European Heart Journal,2006,27:1174-1181.
[21]William John Martin, Michaela Walton, Jacquie Harper. Resident Macrophages Initiating and Driving Inflammation in a Monosodium Urate Monohydrate Crystal-Induced Murine Peritoneal Model of Acute Gout [J]. Arthritis & Rheumatism,2009,60(1):281-289.
[22]Charles J. Roberge, Rinalda de MCdicis, Jean Michel Dayer, et al. Crystal-induced neutrophil activation. V. Differential production of biologically active IL-1 and IL-1 receptor antagonist [J]. The Journal of Immunology, 1994,152(11):5485-5494.
[23]Philippe Desaulniers, Maria Fernandes, Caroline Gilbert, et al. Crystal-induced neutrophil activation. Ⅶ. Involvement of Syk in the responses to monosodium urate crystals [J]. Journal of Leukocyte Biology,2001,70(4):659-668.
[24]C. Schiltz, F. Liote, F. Prudhommeaux, et al. Monosodium Urate Monohydrate Crystal-Induced Inflammation In Vivo[J]. Arthritis & Rheumatism,2002,46(6): 1643-1650.
[25]Carle Ryckman, Shaun R. McColl, Karen Vandal, et al. Role of S100A8 and S100A9 in Neutrophil Recruitment in Response to Monosodium Urate Monohydrate Crystals in the Air-Pouch Model of Acute Gouty Arthritis[J]. Arthritis & Rheumatism,2003,48(8):2310-2320.
[26]D R Blake, N D Hall, P A Bacon, et al. Effect of a specific iron chelating agent on animal models of inflammation [J]. Ann Rheum Dis,1983,42:89-93.
[27]Pandey S. Various techniques for the evaluation of anti arthritic activity in animal models[J]. J Adv Pharm Tech Res,2010,1:164-71.
[28]Evan Prince Sabina, Shruthi Nagar, Mahaboobkhan Rasool. A Role of Piperine on Monosodium Urate Crystal-Induced Inflammation-An Experimental Model of Gouty Arthritis[J]. Inflammation,2011,34(3):184-192.
[29]Charles W. Denko, Mark Petricevic. Sympathetic or reflex footpad swelling due to crystal-induced inflammation in the opposite foot[J]. Inflammation, 1978,3(1):81-86.
[30]U. A. S. Al Khalidi, T. H. Chaglassian. The species distribution of xanthine oxidase[J]. Biochem J,1965,97(1):318-320.
[31]Jingqun Huang, Siwang Wang, Miaozhang Zhu, et al. Effects of Genistein, Apigenin, Quercetin, Rutin and Astilbin on serum uric acid levels and xanthine oxidase activities in normal and hyperuricemic mice[J]. Food and Chemical Toxicology,2011,9(49):1943-1947.
[32]James J. Carroll, Holly Coburn, Roberta Douglass, et al. A Simplified Alkaline Phosphotungstate Assay for Uric Acid in Serum[J]. Clinical Chemistry, 1971,17(3):158-160.
[33]Jyh-Myng Zen, Jia-Jen Jou, Govindasamy Ilangovan. Selective voltammetric method for uric acid detection using pre-anodized Nafion-coated glassy carbon electrodes[J]. Analyst,1998,123:1345-1350.
[34]Su-Hua Huang, Yu-Chuan Shih, Chung-Yu Wu, et al. Detection of serum uricacid using the optical polymeric enzyme biochip system[J]. Biosensors and Bioelectronics,2004,19(12):1627-1633.
[35]S.K. George, M.T. Dipu, U.R. Mehra, et al. Improved HPLC method for the simultaneous determination of allantoin, uricacid and creatinine in cattle urine[J]. Journal of Chromatography B,2006,832(1):134-137.
[36]Bernhard Widner, Ernst R. Werner, Harald Schennach, et al. Simultaneous Measurement of Serum Tryptophan and Kynurenine by HPLC[J]. Clinical Chemistry,1997,43(12):2424-2426.
[37]郁颖佳,郑晓伟,黄滔敏,等.高效液相色谱法测定人体血浆中尿酸的浓度[J].复旦学报(医学版),2006,33(2)：273-275.
[38]D. W. Warnock, M. D. Richardson, A. Turner. High performance liquid chromatographic (HPLC) and other non-biological methods for quantitation of antifungal drugs[J]. Journal of Antimicrobial Chemotherapy,1982,10:467-478.
[39]刘二刚,傅旭春,钱莺,等.柱前衍生HPLC法测定大鼠肾组织中羟脯氨酸的含量[J].浙江大学学报(医学版),2012,41(2)：188-191.
[40]E. Cendejas-Bueno, A. Forastiero, J. L. Rodriguez-Tudela, et al. HPLC/UV or bioassay:two valid methods for posaconazole quantification in human serum samples[J]. Clinical Microbiology and Infection,2011:1-7.
[41]H. Ralph Schumacher. The pathogenesis of gout[J]. Cleveland Clinic Journal of Medicine,2008,75(sup15):S2-S4.
[42]Jiyuan Zhao, Qionglin Liang, Guoan Luo, et al. Purine Metabolites in Gout and Asymptomatic Hyperuricemia:Analysis by HPLC-Electrospray Tandem Mass Spectrometry[J]. Clinical Chemistry,2005,51(9):1742-1744.
[43]Juan G. Puig, Fel i citas A. Mateos, Manuel L. Jim e nez, et al. Renal excretion of hypoxanthine and xanthine in primary gout[J]. The American Journal of Medicine, 1988,85(4):533-537.
[44]William R. Wilcox, Ali Khalaf. Solubility of uric acid and monosodium urate[J]. Med. & Biol. Eng,1972,10:522-531.
[45]Fires J. S., Mccarty D. J., Jr. Acute synovitis in normal joints of man and dog produced by injections of microcrystalline sodium urate, calcium oxalate and corticosteroid esters[J]. Arthritis & rheumatism,1962(5):295.
[46]Paulding Phelps, Daniel J. McCarty. Crystal-Induced Inflammation in Canine Joints Ⅱ. Importance of Polymorphonuclear Leukocytes[J]. JEM, 1966,124(1):115-126.
[47]Darshna R. Yagnik, Betsy J. Evans, Oliver Florey, et al. Macrophage Release of Transforming Growth Factor β 1During Resolution of Monosodium Urate Monohydrate Crystal-Induced Inflammation[J]. Arthritis & Rheumatism, 2004,50(7):2273-2280.
[48]P. T. Chapman, F. Jamar, A. A. Harrison, et al. Characterization of E-selectin expression, leucocyte traffic and clinical sequelae in urate crystal-induced inflammation:An insight into gout[J]. British Journal of Rheumatology, 1996,35:323-334.
[49]Joel R. Pittman, Michael H. Bross. Diagnosis and management of gout[J]. American family physician,1999,59(7):1799-1806.
[50]国家药典委员会.中华人民共和国药典(一部)[M].北京：化学工业出版社,2010：250-251.
[51]楼芳嫣.中药穿地龙的研究进展[J].中国药师,2010,7(13)：1041-1043.
[52]高菁,李靖,于秀辰.商宪敏教授论治痛风经验[J].北京中医药大学学报(中医临床版),2005,12(3)：30-31.
[53]张伟锋,刘宝山.薯蓣皂苷的药理作用研究进展[J].世界中西医结合杂志,2010,5(6)：543-545.
[54]Bonifacio A'lvarez Lario, Jesu's Macarron Vicente. Uric acid and evolution[J]. Rheumatology,2010,49:2010-2015.
[55]Yan Shi, Ashley D. Mucsi, Gilbert Ng. Monosodium urate crystals ininflammation and immunity[J]. Immunological Reviews,2010(233):203-217.
[56]Fabio Martinon, Laurie H. Glimcher. Gout:new insights into an old disease[J]. The Journal of Clinical Investigation,2006,116(8):2073-2075.
[57]Sanjeev Mariathasan, Denise M. Monack. Inflammasome adaptors and sensors:intracellular regulators of infection and inflammation[J]. Immunology, 2007,1(7):31-40.
[58]R Terkeltaub, J S Sundy, H R Schumacher, et al. The interleukin 1 inhibitor rilonacept in treatment of chronic gouty arthritis:results of a placebocontrolled, monosequence crossover, nonrandomised, single-blind pilot study [J]. Ann Rheum Dis,2009,68:1613-1617.
[59]Charles A. Dinarello. Anti-inflammatory Agents:Present and Future[J]. Cell, 2010,140:935-950.
[60]M. Miyata, H. Ohira, S. Suzuk, et al. Significance of low mRNA level of interleukin-4 and-10 in mononuclear cell of the synovial fluid of patients with rheumatoid arthritis[J]. Clin Rheumatol,2000,19:365-370.
[61]F. M. Cicuttini, K. A. Byron, D. Maher, et al. Serum IL-4, IL-10 and IL-6 in inflammatory arthritis [J]. Rheumatol Int,1995,14:201-206.
[62]Yousuke Murakami, Tohru Akahoshi, Shinichi Kawai, et al. Antiinflammatory Effect of Retrovirally Transfected Interleukin-10 on Monosodium Urate Monohydrate Crystal-Induced Acute Inflammation in Murine Air Pouches[J]. Arthritis & Rheumatism,2002,46(9):2504-2513.
[63]James M. Woods, Kenneth J. Katschke, Jr., et al. IL-4 Adenoviral Gene Therapy Reduces Inflammation, Proinflammatory Cytokines, Vascularization, and Bony Destruction in Rat Adjuvant-Induced Arthritis[J]. J Immunol, 2001,166:1214-1222.
[64]Fietta P, Delsante G. The effector T helper cell triade. Rivista di biologia[J]. Jan-Apr,2009,102(1):61-74.
[65]Shu Lin Chang, Yi Ming Chiang, Cicero Lee Tian Chang, et al. Flavonoids, centaurein and centaureidin, from Bidens pilosa, stimulate IFN- Y expression [J]. Journal of Ethnopharmacology,2007,112:232-236.
[66]Xu Qiang, Sun Yang. Novel Immunosuppression Stemming from the Selective Activity of Chinese Herbal Grugs[J]. Progress in Chemistry,2009,21(1):55-62.
[67]宋少华,沈筱云,丁国善,等.落新妇苷对小鼠骨髓来源树突状细胞成熟及免疫功能的抑制作用[J].中西医结合学报,2010,8(2)：145-151.
[68]陈涛,潘铁成,高思海,等.落新妇甙对小鼠心脏移植排斥反应的抑制作用[J].山东医药,2006,46(33)：7-8.
[69]Mingjian Fei, Xuefeng Wu, Qiang Xu. Astilbin inhibits contact hypersensitivity through negative cytokine regulation distinct from cyclosporin A[J]. Journal of Allergy and Clinical Immunology,2005,116(6):1350-1356.
[70]Hong wei Yi, Xiao min Lu, Feng Fang, et al. Astilbin inhibits the adhesion of T lymphocytes via decreasing TNF-αand its associated MMP-9 activity and CD44 expression[J]. International Immunopharmacology,2008:1467-1474.
[71]Yu Cai, Ting Chen, Qiang Xu. Astilbin suppresses delayed-type hypersensitivity by inhibiting lymphocyte migration[J]. Journal of Pharmacy and Pharmacology, 2003,55(5):691-696.
[72]Y. Cai, T. Chen, Q. Xu. Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes[J]. Inflamm. Res,2003,(52):334-340.
[73]赵金平,李平,张韵凤,等.转化生长因子β 1对心脏移植排斥反应中细胞黏附分子表达的影响[J].华中科技大学学报(医学版),2009,29(2)：212-214.
[74]林慧庆,王建军,唐建,等.落新妇甙对大鼠肺移植排斥反应的抑制作用[J].微循环学杂志,2008,18(2)：8-9.
[75]高思海,李平,陈涛,等.落新妇甙对心脏移植排斥反应中细胞因子表达的影响[J].中华小儿外科杂志,2006,(2)：87-89.
[76]J. D. L. Wilhelm. Mechanisms responsible for increased vascular permeability in acute inflammation[J]. Inflammation Research,1973,3(5):297-306.
[77]D. L. Wilhelm, Brenda Mason. Vascular permeability changes in inflammation: The role of endogenous permeability factors in mild thermal injury[J]. Br J Exp Pathol,1960,41 (5):487-506.
[78]G. Logan, D. L. Wilhelm. Vascular permeability changes in inflammation:Ⅱ. The effect of lecithinase antagonists in ultraviolet injury in the guinea-pig[J]. Br J Exp Pathol,1966,47(4):324-330.
[79]Robert Paul, Uwe Koedel, Frank Winkler, er al. Lack of IL-6 augments inflammatory responses but decreases permeability in bacterial meningitis[J]. Brain,2003,126:1873-1882
[80]Sumagin R, Lomakina E, Sarelius I H. Leukocyte-endothlial cell interactions are linked to vascular permeability via ICAM-1-mediated signaling[J]. Am J. Phsiol Heart Circ Physiol,2008,19:H969-H977.
[81]N. A. Klimenko, E. A. Pavlova. Role of leukocytes in increased vascular permeability in inflammation[J]. Bluletin of experimental biology and medicine, 1998,128(2):800-802.
[82]Pascale Chomarat, Edouard Vannier, Julie Dechanet, et al. Balance of IL-1 Receptor Antagonist/1L-1 β in Rheumatoid Synovium and Its Regulation by IL-4 andIL-10[J]. The Journal of Immunology,1995:1432-1439.
[83]Enver Akalin, Wayne W Hancock, Norberto Perico, et al. Blocking cell microtubule assembly inhibits the alloimmune response in vitro and prolongs renal allograft survival by inhibition of Thl and sparing of Th2 cell function in vivo[J]. Journal of the American Society of Nephrology,1995,5:1418-1425.
[84]Yoshihiko Tanaka, Shinjiro Hamano, Kazuhito Gotoh, et al. T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-a subunit controlled by the Rac activator Dock2[J]. Nature Immunology,2007,8:1067-1075.
[85]Susanne J Szabo, Sean T Kim, Gina L Costa, et al. A Novel Transcription Factor, T-bet, Directs Thl Lineage Commitment[J]. Cell,2000,100:655-669.
[86]Andrew Yatesa, Robin Callarda, Jaroslav Stark. Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiations model for cellular decision-making[J]. Journal of Theoretical Biology,2004,231 (2):181-196.
[87]Ruslan Medzhitov. Inflammation 2010:New Adventures of an Old Flame[J]. Cell, 2010,140:771-776.
[88]John Kanellis, Duk-Hee Kang. Uric acid as a mediator of endothelial dysfunction, inflammation, and vascular disease [J]. Seminars in Nephrology,2005,25(1):39-42.
[89]Loretta Cain, Anoop Shankar, Alan M. Ducatman, et al. The relationship between serum uric acid and chronic kidney disease among Appalachian adults[J]. Nephrology Dialysis Transplantation,2010,25(11):3593-3599.
[90]Marilda Mazzali, Jeremy Hughes, Yoon-Goo Kim, et al. Elevated Uric Acid Increases Blood Pressure in the Rat by a Novel Crystal-Independent Mechanism[J]. Hypertension,2001,11:1100-1106.
[91]Bryan Emmerson. Hyperlipidaemia in hyperuricaemia and gout[J]. Ann Rheum Dis, 1998,57:509-510.
[92]Hyon K. Choi, David B. Mount, Anthony M. Reginato. Pathogenesis of Gout[J]. Ann Intern Med,2005,143:499-516.
[1]Edward Roddy, Michael Doherty. Epidemiology of gout[J]. Arthritis Research & Therapy,2010,12:223.
[2]Diana Rudan, Ozren Polasek, Ivana Kolcic. Uric Acid:the Past Decade[J]. Croat Med J,2010,51:1-6.
[3]Hak. A Elisabeth, Choi. Hyon K. Lifestyle and gout[J]. Current Opinion in Rheumatology,2008,20(2):179-186.
[4]Hanyao Huang, Lawrence J. Appel, Michael J. Choi, et al. The Effects of Vitamin C Supplementation on Serum Concentrations of Uric Acid[J]. Arthritis & Rheumatism, 2005,52(6):1843-1847.
[5]By T. Gibson, R. Waterworth, P. Hatfield, et al. Hyperuricemia, Gout and Kidney Function in New Zealand Maori Men[J]. British Journal of Rheumatology, 1984,23:276-282.
[6]Matthias A. Hediger, Richard J Johnson, Hiroki Miyazaki, et al. Molecular Physiology of Urate Transport[J]. Physiology,2005,20:125-133.
[7]Choi Hyon K, Zhu Yanyan, Mount. David B. Genetics of gout[J]. Current Opinion in Rheumatology,2010,3.22(2):144-151.
[8]Philip L. Riches, Alan F. Wright, Stuart H. Ralston. Recent insights into the pathogenesis of hyperuricaemia and gout[J]. Human Molecular Genetics, 2009,18(2):R177-R184.
[9]J. T. Scott. Drug-induced gout[J]. Bailliere's Clinical Rheumatology, 1991,5(1):39-60.
[10]Angel Lopez Cuenca, Vanessa Roldan, Francisco Marin. Hypouricemic effect of statins:Another pleiotropic benefit[J]. J Thorac Cardiovase S(?)g, 2010,139:1358-1359.
[11]Perez-Ruiz F, Liote F. Lowering serum uric acid levels:what is the optimal target for improving clinical outcomes in gout[J]. Arthritis Rheum,2007,57:1324-1328.
[12]Leslie R Harrold, Susan E Andrade, Becky A Briesacher, et al. Adherence with urate-lowering therapies for the treatment of gout[J]. Arthritis Research & Therapy, 2009,11:R46.
[13]Lada Beara Lasic, Michael H Pillinger, David S Goldfarb. Advances in the management of gout:Critical appraisal of febuxostat in the control of hyperuricemiaInternational[J]. Journal of Nephrology and Renovascular Disease, 2010:3-10.
[14]M K Reinders, E N van Roon, T L Th A Jansen, et al. Efficacy and tolerability of urate-lowering drugs in gout:A randomised controlled trial of benzbromarone versus probenecid after failure of allopurinol[J]. Ann Rheum Dis,2009,68:51-56.
[15]Lee. Ming Han H, Graham. Garry G, Williams. Kenneth M. A Benefit-Risk Assessment of Benzbromarone in the Treatment of Gout:Was its Withdrawal from the Market in the Best Interest of Patients[J]. Drug Safety,2008,31(8):643-665.
[16]Bruce N Cronstein, Robert Terkeltaub. The inflammatory process of gout and its treatment[J]. Arthritis Research & Therapy,2006,8(Suppl 1):S3-S9.
[17]Gim Gee Teng, Raj Nair, Kenneth G. Saag. Pathophysiology, Clinical Presentation and Treatment of Gout[J]. Drugs,2006,66(12):1547-1563.
[18]Yu, Kuang Hui. Febuxostat:A Novel Non-Purine Selective Inhibitor of Xanthine Oxidase for the Treatment of Hyperuricemia in Gout[J]. Recent Patents on Inflammation & Allergy Drug Discovery,2007,1(1):69-75.
[19]Fernando Perez Ruiz, Nicola Dalbeth, Naomi Schlesinger. Febuxostat, a novel drug for the treatment of hyperuricemia of gout[J]. Future Rheumatol,2008,3(5): 421-427.
[20]Mattheus K Reinders, Tim L Th A Jansen. Management of hyperuricemia in gout:Focus on febuxostat[J]. Clinical Interventions in Aging,2010,5:7-18.
[21]Merry R. Sherman, Mark G. P. Saifer, Fernando Perez-Ruiz. PEG-uricase in the management of treatment-resistant gout and hyperuricemia[J]. Advanced Drug Delivery Reviews,2008,60(1):59-68.
[22]Bruno Vogt. Urate oxidase(rasburicase) for treatment of severe tophaceous gout[J]. Nephrol Dial Transplant,2005,20:431-433.
[23]Michael S. Hershfield, L. Jackson Roberts, Nancy J. Ganson, et al. Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo[J]. PNAS,2010,107(32):14351-14356.
[24]John S. Sundy, Michael A. Becker, Herbert S. B. Baraf, et al. Reduction of Plasma Urate Levels Following Treatment With Multiple Doses of Pegloticase(Polyethylene Glycol-Conjugated Uricase) in Patients With Treatment-Failure Gout Results of a Phase Ⅱ Randomized Study[J]. Arthritis & Rheumatism,2008,58:2882-2891.
[25]Krishnan E, Lienesch D, Kwoh CK. Gout in ambulatory care settings in the United States[J]. J Rheumatol,2008,35:498-501.
[26]Hector Bueno, Alfredo Bardaji, Paola Patrignani, et al. Use of Non-Steroidal Antiinflammatory Drugs and Type-Specific Risk of Acute Coronary Syndrome[J]. The American Journal of Cardiology,2009,12:1-5.
[27]N. Lawrence Edwards, Terence Gibson, Robert A. Terkeltaub. Gout Treatment[J]. A Clinician's Pearls and Myths in Rheumatology,2010:361-367.
[28]Robert Terkeltaub. Novel therapies for treatment of gout and hyperuricemia[J]. Arthritis Research & Therapy,2009,11:236.
[29]Alexander So, Thibaut De Smedt, Sylvie Revaz, et al. A pilot study of IL-1 inhibition by anakinra in acute gout[J]. Arthritis Research & Therapy,2007,9:R28.
[30]R Terkeltaub, J S Sundy, H R Schumacher, et al. The interleukin 1 inhibitor rilonacept in placebo-controlled, monosequence crossover, treatment of chronic gouty arthritis:Results of a non-randomised, single-blind pilot study[J]. Ann Rheum Dis,2009,68:1613-1617.
[31]Vikneswaran Murugaiyah, Kit Lam Chan. Mechanisms of antihyperuricemic effect of Phyllan thus niruri and its lignin constituents [J]. Journal of Ethnopharmacology, 2009,124:233-239.
[32]Zhifeng Yu, Wing Ping Fong, Christopher H. K. Cheng. The Dual Actions of Morin as a Hypouricemic Agent:Uricosuric Effect and Xanthine Oxidase Inhibitory Activity[J]. JPET,2006,316(1):169-175.
[33]Xing Wang, Caiping Wang, Qinghua Hu, et al. The dual actions of Sanmiao wan as a hypouricemic agent:Down-regulation of hepatic XOD and renal mURAT1 in hyperuricemic mice[J]. Journal of Ethnopharmacology,2010,128:107-115.
[34]Zuoqi Ding, Yue Dai, Zhengtao Wang. Hypouricemic Action of Scopoletin Arising from Xanthine Oxidase Inhibition and Uricosuric Activity [J]. Planta Med, 2005,71(2):183-185.
[35]Xiaoyu Liu, Ruohua Chen, Yanjun Shang, et al. Lithospermic acid as a novel xanthine oxidase inhibitor has anti-inflammatory and hypouricemic effects in rats[J]. Chemico-Biological Interactions,2008,176(2-3):137-142.
[36]Jieun Lee, Jeongmi An, Hee-Jin Yang, et al. Reparatory and Preventive Effects of Oriental Herb Extract Mixture(OHEM) on Hyperuricemia and Gout[J]. Food Sci. Biotechnol,2010,19(2):517-524.