摘要
研究目的 急性痛风性关节炎是骨科常见病、疑难病之一。近年来,随着我国人民生活水平的提高及饮食结构的改变,痛风性关节炎在我国的发病率有明显的上升趋势,发病率在3‰左右,相当于癌的发病率,且严重地影响着人们的身体健康和生活质量。在本病的治疗上,西医多采用消炎、止痛、抑制血尿酸形成或(和)促进血尿酸排泄及对症治疗,但因其有明显的毒副作用,且停用后易复发,故在一定程度上限制了它们的应用。四黄水蜜由广东省中医院研制生产,在治疗湿热型病症所致疼痛方面,有良好疗效。而四妙散乃治疗痛风的基础方,临床疗效显著。本研究旨在探讨四黄水蜜外敷合加味四妙散内服的方法治疗急性痛风性关节炎的临床疗效,从而为急性痛风性关节炎的治疗开辟一条安全有效的新途径。
研究方法 本研究将65例符合纳入标准的患者随机分为两组,治疗组予以加味四妙散内服及四黄水蜜外敷,对照组予以秋水仙碱口服。参照《中药新药临床研究指导原则》对急性痛风性关节炎患者的症状、体征进行分级,并制定急性痛风性关节炎观察表,一周后按观察表计分做统计学处理,进行治疗前后比较及组间比较。对纳入本研究的急性痛风性关节炎患者进行体温(T)、血尿酸(UA)、白细胞计数(WBC)、关节疼痛、关节压痛、关节功能、综合疗效、不良反应等方面的评估。
结果 研究结果表明两组疗效相当:治疗组总有效率为90.9%,对照组总有效率为90.6%,经Ridit检验(P>0.05),差异无统计学意义。两组患者治疗前后症状和体征积分及实验室指标的比较,除对照组的血尿酸治疗前后比较(P>0.05)外,其余指标治疗前后比较(P<0.01),治疗后结果明显优于治疗前。组间血尿酸水平比较(P<0.05),治疗组疗效优于对照组,其余指标组间比较(P>0.05),两组无显著性差异。整个研究过程,治疗组无一例出现不良反应;对照组有5例患者出现不良反应:其中胃脘部不适者2例,安全级别为3级,经对症处理后可继续给药;肾功能异常者3例,安全性分级均为2级,无需处理后好转,可继续给药。
结论 本研究结果表明,通过应用四黄水蜜外敷合加味四妙散内服治疗急性痛风性关节炎,确实能起到降体温、消肿止痛、改善关节功能、降低血尿酸的作用,且未发现有明显的临床毒副作用,故值得临床推广。
ObjeciveAcute gouty arthritis is a common disease and stubborn disease in orthopedics. Along with the elevation of living standard and the changing of food and drink structure, the morbility of acute gouty arthritis increases year by year. In the recent years the morbility of acute gouty arthritis is about 3%o and corresponds to the cancerous incidence. Acute gouty arthritis has impacted human healthy and quality of life severely. In the treatment of this disease, the medical doctors used to apply dephlogisticate or alliviate and symptomatic treatment, but for their apparente poison and side effect and also for the recurrence of this disease after drug withdraw. So in some degree, the application of these drugs is limited. The Sihuangshuimi is manufactured and produced by the Guangdong hospital of Chines Tradictional Medicine. It has a good curative effect in the therapy of humid heat type disease. Simiaosan is an empirical formula in the treatment of acute gouty arthritis. It is aplplied to treat acute gouty arthritis frequently and got significant clinical curative effect. The research objective is to investigate the clinical curative effect about the oral administration of Simiaosan jiawei combined with the external application of Sihuangshuimi in the treatment of acute gouty arthritis and to seek for a safe and valid program for it. MethodsAll the 65 patients of acute gouty arthritis were choosen from the patients from out-patients' clinic or in-patient of the Guangdong Hospital of TCM. And all the patients consistent with the internalize standard were randomly divided into two groups. The treament group was treated by simiaosan jiawei and combined with the external apllication of Sihuanhuimi. The control group
was treated by Qiushuixianjian. Then reference to the ((New Traditional Chinese Medicine Clinical Study Direction Principle )) made a observation table according to patients' grade of acute gouty arthritis symptoms and physical sign. After a week, all the acquired data were done statistical treatment, and carried out prior treatment and post-treatment comparision and group comparison. To evaluate the blood uric acid (BUA), the temperature (T), the lencocyte count (WBC), the joint function, the comprehensive curative effect, and side effects etc of these patients. ResultsThe therapies of two groups are equivalence. The total effective rate of treament group is 90.9%, the control group is 90.6%. After been examined by Ridit analysis (P>0. 05), the difference between two groups has not statistical significant. Comparing the symptoms and physical sign' integral of patients before treatment and post treatment, except for the BUA of control group has not statistical significant (P>0. 05) , all the other indexs have statistical significant (P<0. 01) , the results of before treatment are better than that of post treatment obviously. The comparison between two groups, except for BUA of the treament group has an advantage to the control group (P<0. 05) , the other indexs have not statistical significant between two groups (P> 0. 05) . There are no cases to appear side effect in treament group. The control group has 5 patients to show up side effect. Among them, there are 2 patients not well with their stomaches, safety rating for 3 Class, and they can keep on this research after treated according to their symptoms. Besides of it the other 3 patients appear kidney function abnormality, safety rating for 2 Class, but their kiney funtion can change to nomal level without any special treatment, and all of them can keep on this research. Cone I us i onThe effect of using sihuangshuimi combined with simiaosan jiawei to cure acute gouty arthritis is not only to improve joint fuction and cut down BUA leval obviously, but also to decline the body temperature^ decrease swelling and to relieve pain. Moreover it has no any side effect. It is a safe and effective therapeutic regiment for gout.
引文
[1] 何泽民.镇痛息风汤治疗急性痛风性关节炎40例临床观察[J].中华实用中西医杂志,2004;4,(17):3284—3285.
[2] 肖玉兰.痛风性关节炎[J].人民军医,1995;2(4):52.
[3] 张振文,尹潍,王正伦,等.痛风的危险因素[J].国外医学内分泌学分册,1997;17(3):141.
[4] 黄迅,焦一伟.痛风性关节炎25例临床分析[J].颈腰痛杂志,1997;18(3):165.
[5] 余新明.克痛定汤治疗急性痛风51例疗效观察[J].中国中医药信息杂志,2000;7(12):60.
[6] 国家中医药管理局《中华本草》编委会.中华本草精选本[M],上海:上海科学技术出版社,1996,第1版:1042、1888、404、2140.
[7] 郭子光.现代中医治疗学[M],成都:四川科学技术出版社,1997,第1版:924.
[8] 王必中.浅述中医对痛风的认识及治疗[J].安徽中医学院学报,1992;11(3):12.
[9] 解围华.中医药治疗痛风性关节炎的研究[J].北京中医杂志,2002;21(4):122.
[10] Darmawan J, Valkenburg HD. Theep idemiology of gout and hyperuricemia in a rural population of Java[J].J Rheumatology, 1992;19 (10):1595—1599.
[11] 蒋明,朱立平,林孝义,等.风湿病学[M],北京:科学出版社,1995,第1版:1470.
[12] 徐晓菲,姜宝法,张源潮,等.山东沿海地区人群血尿酸水平及其在痛风筛检中的意义[J].中国公共卫生,1999;15(3):205—206.
[13] 杜蕙,陈顺乐,王员,等.上海市黄浦区社区高尿酸血症与痛风流行病学调查[J].中华风湿病学杂志,1998;2(2):75—78.
[14] Star VL. Prevention and management of gout[J].Drugs, 1983, (45):212.
[15] Diepper PA. Investigation and management of gout in the young and the elderly [J].Ann Rheum Dis, 1991: 10(50):263.
[16] Zuo M, Nishio H, Lee M J, et al. The C677T mutation in the methylene tetrahydrofolate reductase gene increases seumuric acid in elderly men[J].J Hum Genet, 2000: 5(45):257—262.
[17] Hayashi H, Nagasaka S, Ishikawa S, et al. Contribution of a missense mutation(Trp64Arg) in beta3-adrenergic receptor gene to multiple risk factors in Japanese men with hyperuricemia[J]. Endocr J, 1998;5(45):779-784.
[18] Ko YC, Wang TN, Tsai LY, et al. Chang Shun Jen High prevalence of hyperuricemia in adolescent Taiwan aborigines[J]. J Rheumatology, 2002;29(4):837—842.
[19] 叶任高.内科学[M],北京:人民卫生出版社,2001,第5版:877.
[20] 孟昭亨.痛风[M],北京:北京医科大学、中国协和医科大学联合出版社,1997,第1版:19—30.
[21] Ramirez D, Dame B, Lombrail P, et al. The prevalence of a alcoholic disease[J].At a teaching hospital of the Paris suburbs (Frech), 1990;19(34):1571—1575.
[22] Yamaanaka H, Kamatani N, Hakoda M, et al. Analysis of the genotypes for aldehyde dehydrogenase2 in Japanese patients with primary gout[J].Adv Exp Med Biol, 1994;370(10):53—56.
[23] Roubenoff R, Klog MG, Mead LA. Incidence and risk factors for gout in white men[J]. JAMA, 1991:266(4):3004—3007.
[24] Wortmann RL. Gout and hyperuricemia[J]. Curr Opin Rheumatol, 2002;14(13):281—286.
[25] 高岱、刘元禄、刘挺,等.中汇痛风定胶囊对急性痛风性膝关节炎家兔模型滑膜组织环氧化酶2影响的实验研究[J].中医正骨,2004;4(16):6—7.
[26] Mastsukawa A, Yoshimura T, Kazuhiko Miyamoto, et al. Analysis of the inflammatory cytokine network among TNF-α IL-β IL-receptor an-tagonist and IL-8 in Lps-Induced rabbit arthritis[J].Laboratory Investigation, 1997;76(5):629.
[27] Mastsukawa A, Yoshimura T, Maeda T, et al. Analysis of the cytokine network among tumor necrosis factor alpha, interleukin-I beta, interleukin-8 and interleukin-I receptor antagonist in monosodium urate crystal-induced rabbit arthritis[J].Lab Invest Japan, 1998;78(5):559-569.
[28] Terkeltaub R, Zqchariac C, Santoro D, et al. Monoctre-derived neutrophil chemotatic factor, interleukin 8 is a potential mediator of crystal-induced inflammation[J].Arthritis Rheum, 1991;18(34):894—903.
[29] Rampart M, Herman AG, Grillet B, et al. Development and application of a radioimmunology for interloukin-8: detection of interloukin-8 in synovial fluids from patients with inflammatory joint disease[J].Lab Invest, 1992;15(66):512.
[30] Ko Y, Mudaida N, Panyutich A, et al.A Sensitive enzyme linked immunosorbent assay for human interloukin-8[J].J Immunol Methods, 1992;36(149):227.
[31] Johason K, Aorden L, Choi Yit. The proinflammatory cytokine response to coagulation and endotoxin in whole blood[J].Blood, 1996;25(87):5051.
[32] 孟昭亨.痛风[M],北京:北京医科大学、中国协和医科大学联合出版社,1997,第 1版:90.
[33] 陈文照.痛风宁对尿酸钠致大鼠关节炎下丘脑单胺类神经递质的影响[J].中国中医骨伤杂志,2001;9(1):17.
[34] 张乃峥.临床风湿病学[M],上海:上海科技出版社,1999,第1版:371—373.
[35] 张春珍.关于嘌呤饮食对痛风性关节炎的治疗作用[J].中国临床康复,2002;6(11):1680.
[36] 范锦娣,励如波.痛风的饮食指导[J].时珍国医国药,2003;14(7):441.
[37] 郁采蘩.痛风[J].中华内科杂志,1981;1(1):51—56.
[38] 张史昭,黄蔚霞,李学,等.痛风洗剂对尿酸钠诱导大鼠痛风性关节炎的防治作用[J].中国中医药科技,2001;8(3):154.
[39] Foreign. Medical Sciences[J].Section on Pharmacy, 1996;23(6):350.
[40] 窦存瑞.双氯芬酸钠治疗急性痛风性关节炎疗效观察[J].甘肃医药,1994;13(4):195.
[41] 鞠世生.消炎舒松-A加普鲁卡因局封治疗痛风8例报道[J].江苏预防医学,1997;8(2):9.
[42] 余存.青霉素治疗痛风30例临床分析[J].综合临床医学,1996;12(2):108.
[43] 劳泉林.氦—氖激光药物综合治疗急性痛风性关节炎对照观察[J].中华理疗杂志,1997;20(4):244.
[44] 张生.痛风侵犯全身关节1例报道[J].中华骨科杂志,1996;16(1):10.
[45] 倪磊,吕厚山,寇伯龙,等.晚期痛风石患者的手术治疗[J].中华骨科杂志,1996;16(1):34—36.
[46] 朴哲,王丹.痛风石晚期的手术治疗[J].吉林医学院学报,1997;17(4):55—56.
[47] 张普国,黄必留.多关节晚期痛风石的手术治疗[J].中华骨科杂志,2000;16(7):548—549.
[48] 张开富.痛风石的手术治疗[J].中华骨科杂志,1996;16(1):63.
[49] 龙道畴.痛风结石的外科治疗[J].实用外科杂志,1987;7(10):535.
[50] 王燕青.当归芍药散治疗痛风的体会[J].实用中西医杂志,1997;13(2):1257.
[51] 程海文.四妙散加减治疗痛风体会[J].肇庆医学,2003;2(3):8—11.
[52] 贾仰春.中西医结合治疗痛风性关节炎32例[J].广西中医药,2001;2(2):25—26.
[53] 田泽芬.中医药治疗痛风性关节炎的现状与展望[J].中国自然医学杂志,2003;5(2):126—128.
[54] 王承蓥.加味四物汤治疗痛风15例[J].中国中西医结合杂志,1993;13(10):628.
[55] 钱忠权.四妙丸加味合新癀片治疗痛风性关节炎50例[J].浙江中医杂志,1995; 2(5):204.
[56] 王训国.加味三妙丸治疗急性痛风性关节炎24例观察[J].湖北中医杂志,1996:18(1):17.
[57] 夏涵.当归拈痛汤加减治疗痛风40例疗效小结[J].中医杂志,1987;28(2):60.
[58] 陈国定.辨证论治痛风性关节炎42例[J].湖北中医杂志,1996;18(1):40.
[59] 朱元芳.中西医结合治愈痛风1例[J].中西医结台杂志,1987;5(7):330.
[60] 张炳球.中西医结合治疗痛风性关节炎32例[J].中国骨伤,1996;9(2):58.
[61] 周太廷.板蓝根注射液治疗痛风5例报告[J].中西医结合杂志,1990;10(12):728.
[62] 姚淮芳.雷公藤治疗急性痛风性关节炎11例报告[J].中西医结合杂志,1990;10(12):728.
[63] 李嫒、陈静.灯盏花注射液治疗痛风急性期疗效观察(附49例病例报告)[J].成都中医药大学学报,1998;21(3):26—27.
[64] 宋文冲,陈超.虎参痛风胶囊治疗痛风20例疗效分析[J].国医国药,2003;14(12):751—752.
[65] 赵兆琳,王义成,李厚铨,等.奚氏痛风灵治疗原发性痛风与肾损害的临床观察[J].上海中医药杂志,2001;35(10):13—14.
[66] 关玉波,赵树森,刘振华,等.痛风定加中药外敷治疗痛风性关节炎的临床观察[J].中医药学报,2002;30(1):14.
[67] 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.
[68] 苏友新,陈伟宏,陈凡,等.痛风宁颗粒治疗慢性痛风性关节炎30例临床研究[J].福建中医学院学报,2003;13(3):12.
[69] 苏友新,陈伟宏,陈凡,等.痛风宁颗粒对30例慢性痛风性关节炎患者血尿酸、血沉、血脂、血流变的影响[J].中国中医骨伤科杂志,2005;13(1):16—18.
[70] 苏友新,陈伟宏,郑良朴,等.痛风宁颗粒对高嘌呤物质所致小鼠—过性高尿酸血症的作用[J].福建中医学院学报,2004;14(4):27—29.
[71] 宋生祥.针拨治疗痛风性关节炎30例[J].上海针灸杂志,1996:15(1):15.
[72] 文绍敦.火针放血治疗痛风105例疗效观察[J],中国针灸,1996;2(3):23.
[73] 吴自力.针刺小肠俞对痛风镇痛效果观察[J].四川中医,1994;8(10):54.
[74] 洋祟军.消肿膏治疗痛风性关节炎35例[J].中国中医骨伤杂志,1990;6(5):29.
[75] 谢东升.虎杖膏外敷治疗痛风性关节炎50例[J].浙江中医杂志,1995;2(5):204.
[76] 张史昭,马红珍.痛风洗剂治疗痛风性关节炎85例临床研究[J].中医杂志,2001;42(6):347—349.
[77] 晏建立,陈繁荣,王新建,等.乐尔膏穴位贴敷治疗痛风性关节炎疼痛60例[J].新中医,2000;32(6):22—23.
[78] 兰玛.痛风汤内服配合芦荟外敷治疗痛风性关节炎36例[J].四川中医,2001;19(9):22—23.
[79] 庞学丰.中药内服结合外洗治疗痛风性关节炎疗效观察[J].广西中医药,2002;25(3):8—10.
[80] 杨忠进.中医辨证治疗痛风256例临床体会[J].中华今日医学杂志,2004;4(3):67.
[81] 国家中医药管理局.中医病证诊断疗效标准[M],南京:南京大学出版社,1994,第1版:60.
[82] 顾新,佟方,李京平,等.疼痛的评定[J].现代康复杂志,2000;4(1):86—87.
[83] 郑筱萸.中药新药临床研究指导原则[M],北京:中国医药科技出版社,1995,第2版:179.
[84] 南云生,毕晨蕾.炮制对黄柏部分药理作用的影响[J].中药材,1995;18(2):81~84.
[85] Resch M, Heilmann J, Steigel A, et al. Further phenols and polyacetylenes from the rhizomes of Atractylodes lancea and their anti—inflammatory activity[J]. Planta Med, 2001;67(5): 437.
[86] Resch M, Steigel A, Chen ZL, et al. 5-Lipoxygenase and cyclooxygenase-1 inhibitory active compounds from Atractylodes lancea[J]. J Nat Prod, 1998;61(3): 34.
[87] 周德文,周立勇.188术类的药理和药效[J].国外医药:植物药分册,1996;11(3):120—122.
[88] 张明发,沈雅琴,朱自平,等.薏苡仁镇痛抗炎抗血栓形成作用的研究[J].基层中药杂志,1998;12(2):34.
[89] 江苏新医学院编.中药大辞典(上册)[M],上海:上海科技出版社,1974,第1版:874.
[90] 王文莉.90年代痛风的中医药治疗概况[J].中医药研究,1995;2(5):58.
[91] 高昌琨,高建,马如龙,等.牛膝总皂苷抗炎、镇痛和活血作用的研究[J].安徽医药,2003;7(4):248—249.
[92] 吴丽明,张敏.土茯苓中落新妇甙的利尿和镇痛作用[J].中药材,1995;18(12):627—630.
[93] 时乐,徐立,尹莲.四种不同加味四妙散抗实验性痛风作用的比较[J].南京中医药大学学报,2005;21(2):106—107.
[94] 罗中华,黄文华,刘敬.几种中药对烫伤小鼠中性粒细胞的作用[J].解放军医学杂志,1994;19(4):271—272.
[95] 李文,殷小杰,廖福龙,等.六种产地赤芍对大鼠抗凝血及抗血小板聚集作用的 比较[J].中国实验方剂学杂志,2001;7(6):30—31.
[96] 黄九兵.大黄在临床热病中的疗效观察[J].中西医结合杂志,1992;(3):46.
[97] Suzuki H,Takaboshi K,Kawakami T,et al.对由炎症刺激引起的巨噬细胞和肝肿瘤细胞NO生成的抑制作用[J].和汉医药杂志,1996;13(2):165.
[98] Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition of activator protein-1 activity by berberine in human hepatoma cells[J].Planta Med, 1999;65(4):381.
[99] Chung CP, Park JB, Bae KH, et al. Pharmacological effects of methanolic extract from the root of Scutellaria baicalensis andits flavonoids on human gingival fibroblast[J]. Planta Med, 1995;61(2):150—154.
[100] 程国强,冯年平,唐琦文,等.黄芩甙对眼科常见病原茵的体外抗茵作用[J].中国医院药学杂志,2001;21(6):384—385.
[101] 田代华.实用中医对药方[M],北京:人民卫生出版社,2000,第3版:687—690.
[102] 王建.中医药学概论[M],北京:人民卫生出版社,2003,第5版:145.
[103] 吕燕,邱全瑛.黄柏对小鼠DTH及其体内几种细胞因子的影响[J].北京中医药大学学报,1999;22(6):48—50.