摘要
目的:(1) 总结中医对IgA肾病的认识及现代研究进展。(2) 结合IgA肾病的病理损害、临床表现及实验室检测值,从客观的微观、宏观方面进行本病中医证的标本虚实、虚实夹杂之证的基本内容,探讨IgA肾病的中医证的实质和变化规律。(3) 从IgA肾病中医辨证论治的临床疗效,评价相关治疗方法,从而更好地指导临床诊疗。
方法:(1) 文献研究:通过查阅古代和现代,国内和国外有关IgA肾病的研究文献,对IgA肾病的中西医研究状况进行总结和评价。(2) 证型及其变化规律的研究:①以Memphis肾活检积分系统指标作为标准,以慢性肾炎中医辩证标准中的主证(症候)及兼夹证(症候)与病理指标作主成分和因子分析,选出最能提示中医证型的病理指标,再将这些指标与标准证型作回归分析,建立各证型回归方程。②以慢性肾炎中医辩证标准中的主证及兼夹证为标准,把IgA肾病主要临床表现(血尿、腰痛、水肿、高血压)和实验室检验值(尿红细胞、尿蛋白、血尿素氮、血肌酐、血清免疫球蛋白A、补体C 3、内生肌酐清除率)作指标,与各标准证型作主成分及回归分析,找出表达证型变化的规律性指标。(3) 临床治疗及其疗效评价研究:根据纳入标准所选患者123例,数字随机,按3:1分为中医治疗组和西医治疗组。中医治疗组根据辨证分型立法施治谴方用药为汤剂,配合雷公藤多甙片。西医治疗组常规西药治疗。二组均3个月为一疗程,视病情继续用药,原则上不超过2个疗程。从治疗前后自身对照和组间对照,比较不同疗法的总疗效、等级疗效、证型症候积分、副作用等差异。
结果:(1) 文献研究:①中医学的认识:IgA肾病没有直接对应的中医病名。中医根据本病的临床表现,归于“尿血”、“腰痛”、“水肿”、“虚劳”、“关格”、“癃闭”等病证范畴。IgA肾病的病因有主因与诱因之分。主因多系脾肾虚损,或阴虚火旺,或阳气亏虚,或阴阳受损。诱因则为外感、湿热、瘀血。实际为本虚标实,虚实夹杂的疾病,病机复杂,病程缠绵。中医药对IgA肾病的治疗取得了较好疗效,归纳起来主要分为辨证分期治疗、辨证分型和专方专药治疗3方面。②现代医学的认识:IgA肾病是一种免疫复合物性肾炎,其发生与遗传及机体免疫系统功能紊乱有关,IgA免疫复合物在肾脏不断沉积损伤肾小球,并通过旁路途径使补体活化,白细胞聚集,炎症细胞激活或肾小球固有细胞活化,释放炎症因子、细胞因子至肾小球损伤。治疗上尚无特殊有效方法,主要以改善临床症状,保护肾功能为基本目的,提倡根据临床表现结合肾脏病理的不同改变分型治疗。(2) 证型及其变化规律的研究:①依据“肾活检积分系统”对123例IgA肾病病理资料,进行主成分分析,找出了表达肾小球变化>85%信息的主要成份,有肾小球硬化、新月体、间质、免疫荧光IgA和C3因子。依据原发性肾小球肾炎中医辩证标准症候资料,进行主成分分析,寻找出了表达证型
Objective:(1) To summarize the knowledge and the new researching development on IgA nephropathy of TCM. (2) By illustrating the basic TCM theory of branch and root, asthenia and sthenia, asthenia accompanied with sthenia on IgA nephropathy from microcosmic and macroscopical point of view by considering the pathologic damage, clinic manifestation and laboratory results to discuss the TCM essential and changing disciplinarian of IgA nephropathy. (3) To evaluate the TCM therapeutic efficacy for IgA nephropathy which is based on the differential diagnosis so as to provide further guidelines for clinical diagnosis and treatment. Method:(1)Literature study: to summarize and assess the researching situation of both TCM and western medicine on IgA nephropathy.(2)Study on patterns and their changing laws:(1) Through considering Memphis renal biopsy assessing system as the standard, and also taking the principal and secondary symptoms and signs of TCM differentiation standard for chronic nephritis as well as pathologic index to make an analyze on main elements and factors in order that the pathologic index which could best refer to the pattern could be chosen, then the regression analyze on the indexes and standard patterns could be made to have regression equations of every patterns. (2)Taking the principal and secondary symptoms and signs of TCM differentiation standard for chronic nephritis as standard, and also taking the main clinic manifestations(hematuria, lumbago, edema and hypertension) and laboratory results (urinary red cell, urinary protein, hemaurea nitrogen, hema cretinine, serum immunoglobulin A, complemen C, creatinine clearance rate) as indexes to make regression analyzes with every standard patterns so as to find out the regularity index which could well express the changing of patterns.(3) Treatment and evaluating the efficacy: 123 patients were chosen
according to the including criteria and divided randomly into TCM group and western medicine group with TCM group is two times of western medicine group. TCM group were treated with herbal soup accompanied with Leigongteng tablets in accordance with differential classification aiming at treatment. Western medicine group were treated with conventional method. Treatment lasted at least 3 months and at most for 6 months for both groups. Comparison were made between two groups on over-all efficacy, efficacy of different level, symptoms and signs grading and side-effects. And comparison were also made between the start and the end of the study. Results:(1) Literature study.? TCM understanding: there is no corresponding name in TCM to IgA nephropathy; According to clinical manifestation, it can be classified into hematuria, lumbago, edema, consumptive disease, guange, dysuria. There are two kinds of cause for the disease, one is principal causes which are kidney and spleen deficiency, deficiency of Yin leads to hyperactivity of fire, Yand and Qi deficiency or damage of both Yin and Yang; the other is predisposing factors such as dampness and heat, hemostasis or attacked by exogenous evils, the essence of which are the root is asthenia and the branch is sthenia and the coexisting of asthenis and sthenia characterized with complicated etiology and long course. TCM therapy on IgA nephropathy has achieved good effects, and its treatment are based on three aspects, differentiating the stage, differentiating the pattern and specific formula. ?Understanding of modern medicine: IgA nephropathy is a kind of immune complex nephritis which is related to genetic and immune system insufficiency. The continuous sedimentation of IgA immune complex cause damage to glomerulus and activate the complements through by-pass, which result in accumulation of leucocyte, inflammatory cell activity or activation of glomerulus cells to release inflammatory factors and cytokine to damage glomerulus. Since there is no special and effective therapy for it, treatment generally focus on improving symptoms and signs and protecting renal function. It is advised to treat according to different types which are categorized by clinical manifestation and pathologic results.(2)Patterns and their changing laws: ? To analyze the main factors of 123 patients according to renal biopsy assessing system to find out the following factors that can reflect more than 85per change of glomeulus, they are glomerulus sclerosis, crescent, stroma, immunofluorescence IgA and C3 factors; to analyze the main factors based on TCM differentiating theory on primary glomerulonephritis to find out the following factors that can reflect
more than 90per change of glomeulus, deficiency pattern: tiresome; Yang deficiency pattern: extremities coldness, white, moist and smooth tongue fur, sunken and thread pulse; Yin deficiency pattern: dry feeling in mouth, red tongue and thread pulse; liver stagnation: impatient and tending to lose temper, bitter mouth, liable to heave a sigh and string pulse; hemostasis: dark tongue proper with hemostasis point; phlegm-wetness pattern: heavy feeling in extremities, fatty tongue fur, anorexia; heat and toxic pattern: sore throat, running sore, yellow and dry tongue fur; dampness and heat pattern: bitter and sticky mouth, fatty and yellow fur. (2) Regression analyze on main factors shows that: Yin deficiency pattern is related to mesangium cell proliferation, glomerulus sclerosis, Fg in immunofluorescence mesangium area and IgG in vascular area; Yang deficiency is related to glomeruius sclerosis, cytocrescent, non-fibrinous adhension, IgM and Fg in immunofluorescence mesangium area with necrosis; Yin and Yang deficiency are with fibrinous glomerulus or fibrinous crescent, fibrinous adhension and Fg in immunofluorescence vascular area. Speaking of sthenic patterns: hemostasis is related to damage of renal tubule and IgG in immunofluorescence mesangium area; heat and toxic pattern is related to mesangum cell increasing, cytocrescent, renal tubule damage and Fg in immunofluorescence area; dampness-phlegm pattern is with fibrinous glomerulus or fibrinous crescent, fibrinous adhensin and IgM in immunofluorescence mesangium area, Fg in vascular area; liver stagnation pattern is related to crescent, clq in immunofluorescence mesangium area and IgA in vascular area. ?Multiple regression and Logistic non-conditional regression analyze indicated that: Yang deficiency of TCM pattern is closely related edema, and the risk for Yang Deficiency in patient with edema is 1. 6 times than the patient without edema; Yin deficiency is related to hematuria, the more obvious the macroscopic hematuria is, the more severe the patient suffer from Yin deficiency, and the risk for Yin deficiency in patient with macroscopic hematuria is 1.5 times of that in patient without; whatever pattern may manifestate lumbago or soreness of loins.(3) Treatment and efficacy evaluation:?0ver~all efficacy: the efficacy of TCM group is 86.04% while that of western medicine group is 51.35%, P=0. 0001.?Efficacy of different grades: complete relieved patient in TCM group are 29(33.72%) and 4 (JO. 81%) in western medicine group, P--0. 016CXO. 05; significantly relieved patient in TCM group are 30(34.88%) and 5 (13.51%) in western medicine group, P=0. 0284<0. 05; improved patient in TCM group are
15(17.44 % ) and 10 ( 27.03 % ) in western medicine group, P=0.3334>0. 05;non-effective patient in TCM group are 12(13.95%) and 18 (36.73 %) in western medicine group, P=0. 0001;(D Efficacy of different patterns: Yin deficiency pattern: complete relieved patient in TCM group are 18(36. 73%) and 0 (0%) in western medicine group; significantly relieved patient in TCM group are 18(36. 73%) and 1 (4. 55 %) in western medicine group; improved patient in TCM group are 10(20.41 %) and 7 (31.82%) in western medicine group; non-effective patient in TCM group are 3(6.12%) and 14 (63.64%) in western medicine group; Speaking of Yang deficiency pattern and both Yin and Yang deficiency patterns, detailed data could' t be gathered because the sample was not big enough. For Yang deficiency pattern, efficacy rate is 81. 25% in TCM groups and 83. 33% in western medicine groups, P = 0. 6116X1 05; For both Yang and Yin deficiency groups, efficacy rate is 71.42% in TCM groups and 66.67% in western medicine groups, P = 0. 8620>0. 05 o?Efficacy of syndromes and signs: comparison made between the start and the end of the study showed that there are significant difference in grading before and after treatment in TCM group whether asthenia or sthenia patterns. In western medicine group, no grading difference for Yin deficiency pattern, however, Yang deficiency asthenia pattern showed decrease in grading after treatment while sthenia pattern is opposite; both Yin and Yang deficiency pattern, Yang deficiency patients' grading reduced but Yin deficiency patients' grading went up and sthenia patterns also had the tendency of increasing. Comparison between two groups showed marked accretion whatever sthenia or asthenia?Toxicity and side-effects: No other side-effects has been detected except two of 86 patients in TCM group had temporarily menstrual disorder and resume normally after quitting Leigongteng tablet. However in western medicine group, 11 of 37 patients emerged with changes of different levels in TCM patterns, such as Yang deficiency relieved with Yin deficiency and dampness heat pattern increased after treated with hormone. Conclusion:(1) Glomerulus sclerosis, crescent, tubule atrophy, vascular pathologic changes, immunofluorescence IgA, C3 can reflect most of the changes in IgA nephropathy(85%), which will be great help for physicians in the treatment and prognosis prediction.(2) The pathology and clinic manifestation of IgA nephropathy is related to TCM differentiating patterns, which contribute to analyze and induce the
引文
[1] 刘宏伟,庞俊娟.中医药治疗IgA肾病探析.辽宁中医杂志,1998;25(4):158.
[2] 胡海翔.IgAN肾病的中西医诊疗进展.中国中医基础医学杂志,1997;3(4):61.
[3] 石庆虹.IgA肾病的中医治疗.四川中医,1999;17(11):11
[4] 时振声.时氏肾脏病学,北京:中国医药出版社.1997,第1版:142～146.
[5] 陈彤梅.洪钦国教授治疗IgA肾病.云南中医中药杂志,2000;21(4):20.
[6] 傅文录,刘宏伟.时振声教授治疗IgA肾病的经验.河南中医,1994;14(6):344～345.
[7] 刘玉宁,邓跃毅,王立红.陈以平教授治疗IgA肾病的临证经验.中国中西医结合肾病杂志,2003;4(6):314～315.
[8] 徐巍,张玉梅.张琪教授对IgA肾病血尿的认识及辨治经验.中国中西医结合肾病杂志,2002;3(4):194～195.
[9] 聂莉芳.IgA肾病血尿的中医辨治.中国中西医结合肾病杂志,2001:2(11):621～623.
[10] 李良.中医辨证论治IgA肾病60例.上海中医药杂志,2002;36(8):24.
[11] 谢天忠,张雷.IgA肾病30例的中医辨证论治.中医杂志,1995;36(4):228.
[12] 杜兰屏,陈以平.中药治疗IgA肾病经验.辽宁中医杂志,2001;28(4):204.
[13] 聂莉芳.IgA肾病血尿的中医辨证体会.中国医药学报,1997;12(3):39.
[14] 刘宏伟.IgA肾病的中医辨证.辽宁中医杂志,1996;23(2):61～75.
[15] 吴竞,杨爱国.清热利湿凉血和络法治疗IgA肾病40例分析.中医药学刊,2003;21(7):1166～1167.
[16] 祝来友,郭云飞.补肾活血化瘀法治疗IgA肾病24例临床观察.新中医,1997;29(5):13.
[17] 杨爱国,安晓英,阮诗玮等.辨证治疗单纯血尿性IgA肾病87例.江苏中医药,2003;24(5):24～25.
[18] 张雪梅,舒贵阳,严晓华.中西医结合治疗IgA肾病疗效观察.中国中西医结合杂志,1996;16(3):172.
[19] 王少亭,宋敏,王耀献等.辨证治疗特发性IgA肾病.北京中医药大学学报,1998;21(4):62.
[20] 聂莉芳,于大君,王洪霞等.益气滋肾冲剂治疗IgA肾病100例临床观察.中医杂志,2002;43(11):843～844.
[21] 胡海翔,贾海骅.滋肾止血片治疗IgA肾病的临床研究.中国中医基础医学杂志,1999;5(2):35.
[22] 薄守洪,鞠建伟.肾宁合剂治疗IgA肾病的临床研究.中国中西医结合杂志,2000;20(10):729.
[23] 宋述菊,高中云.自拟何芪汤治疗IgA肾病临床观察.中医杂志,1999;40(2):89.
[24] 朱起之,柴胡治疗IgA肾病的初步研究.广东医学,2002;23(9):992～993.
[25] 王宇晖,王永钧.110例IgAN肾病中西医结合治疗的临床研究.浙江中医杂志,2000:35(6):256.
[26] 尤永森.中西医结合治疗IgA肾病无症状性血尿疗效观察.现代中西医结合杂志,2003;12(4):359～360.
[27] 洪钦国,罗月中.养阴清热法配合雷公藤制剂治疗IgA肾病57例.新中医,1999,31(10):31～32.
[28] 洪钦国,罗月中.IgA肾病的中医治疗经验.新中医,2003;35(12):31～32.
[29] 李夏玉.火把花根片合益气养阴方剂治疗IgA肾病45例.浙江中医杂志,2000;35(9):472.
[30] 王宇晖,王永钧.110例IgAN肾病中西医结合治疗的临床研究.浙江中医杂志,2000:35(6):256.
[31] 于伟,陈江华.松龄血脉康胶囊合用火把花根片治疗IgA肾病的临床疗效.华西药学杂志,2003;18(3):229～230.
[32] 朱汉威,朱淳,陆玮等.雷公藤多甙长程治疗肾小球肾炎疗效观察.上海第二医科大学学报,2002;22(6):543～544.
[33] 李江涛,许晨,李素等.雷公藤单体T4治疗IgA肾病的实验研究.上海医学,2003;26(S1):19～21.
[34] 叶任高.内科学,北京:人民卫生出版社,2001,第5版:542～544.
[35] 陈惠萍,曾彩虹,胡伟新等.10594例肾活检病理资料分析.肾脏病与透析肾移植杂志,2000:9(6):501～508.
[36] D' AmicoG. Pathogenesis of immunoglobulin A nephropathy. Curt Opin Nephrol Hypertens. 1998; 7: 247～250.
[37] Hsu SI, Winn MP, Oemmer JS, et al. Evidence for genetic factors in the development and progression of IgA nephropathy [J]. Kidney Int, 2000 57(5): 1818～1835.
[38] Liu Z, Yang J, Chen Z, et al. Gene polymorphism in ILl receptor antagonist affects its production by monocytes in IgA nephropathy and Henoch-Schonlein nephritis[J] .Chin Med J, 2001; 114(12): 1313～1316.
[39] 陈香美,柏立群.利用特异性寡核苷酸探针检测IgA肾病HLA-DR基因频率及其临床意义[J].中华医学杂志,1992:72:206.
[40] Zheng F, Kundu GC, Zhang Z, et al. Uterogl. obin is essential in preventing immunoglobulin A nephropathy in mice[J]. Nat Med, 1999; 5 (9): 1018～25.
[41] Endo Y. IgA nephropathy human disease and animal model[J]. Renal Fail, 1997, 19(3): 347～371.
[42] Feehally J, Allen AC. Structural features of IgA molecules which contribute to IgA nephropathy[J]. J Nephrol, 1999: 12(2): 59～65.
[43] De maine AG, Ra mbausek M, Katsutani J, et al. Relation of mesangial IgA glomerulonephritis to polymorphism of immunoglobulin heavy chain switch region. [J]. J Clin Invest, 1998: 81: 611～614.
[44] 黄海燕.肾脏病学,北京:人民卫生出版社,1997年8月,第2版:708～717.
[45] 魏林,刘桂馨,王海燕等.血清IgA-纤维连接蛋白聚合物在IgA肾病诊断中的意义[J].中华内科杂志,1997;36(2):83～86.
[46] Taniguchi Y, Yorika N, Kumagai J, et al .I nte rleukin-6 localization and the prognosis of IgA nephropathy[J]. Nephron, 1999; 81(1): 94～98.
[47] Schena FP. IgA Nephropathies. In: Cameron JS, DavisonAM. Oxford Textbook of Clincal Nephrology. Vol, lst ed, Oxford , Oxford University Press, 1992: 339～369.
[48] Ibels LS, Gyory AZ. IgA nephropathy: Analysis of the natural history, important factors in the progression of renal disease, and a review of the literature. Medicine, 1994: 73: 79.
[49] Lee SMK, Rao VM, Franklin WA et al. IgA nephropathy: Morphologic predictors of progressive renal disease. Hum Pathlo, 1982: 13: 314
[50] Pirani CL, Salinas-Madrigal L. Evaluation of percutaneous renal biopsy. Pathol Annu, 1968: 3: 248.
[51] Clarkson AR, woodroffe AJ, Aarons IA et al. Therapeutic options in IgA nephropathy. Am J Kid Dis, 1988; 12: 443.
[52] OkudaH, Suzuki H, Konishi K et al. Histological alterations in renal specimens as indicators of prognosis of IgA nephropathy. Clin Nephrol, 1992; 37: 235.
[53] Andreoli SP, Bergstein JM. Treatment of severe IgA nephropathy in children. Pediatr Nephrol, 1989; 3: 248.
[54] Andreoli SP, Yum NM, Bergstein JM. IgA nephropathy in children: Significance of glomerular basement membrane deposition of IgA. Am J Nnphrol, 1986; 6: 28.
[55] Wyatt RT, Emancipator SN, Kon V et al. IgA nephropathy databand: development of a system for management of renal biopsy acquired data. Am J Kid Dis, 1997: 6: 817.
[56] 黄海燕.肾脏病学,北京:人民卫生出版社,1997年8月,第2版:717～718.
[57] 吴杰、谭昭.甲基强的松龙冲击治疗合并部分新月体IgA肾病临床观察.中国医师杂志,2003;5(3):326～328.
[58] 张雅君,刘晓渭,陈威等.霉酚酸脂治疗IgA肾病.第四军医大学学报,2003:24(1):73～75.
[59] 陈香美.麦考酚酸脂治疗IgA肾病的随访对照观察.中华医学杂志,2002;82(12):796～801.
[60] 刘洪涛,陈香美,汤力等.尿激酶联合苯那普利治疗IgA肾病的随访对照研究.中华肾脏病杂志.2003;19(4):199～204.
[61] Wyatt RT, Emancipator SN, Kon V et al. IgA nephropathy databand: development of a system for management of renal biopsy acquired data. Am J Kid Dis, 1997; 6: 817.
[62] 中国中医药学会内科学会肾病专业委员会.慢性肾炎中医辩证标准.中医杂志,1996:37(10):627.
[63] 沈庆法.中医临床肾脏病学,上海:上海科学技术文献出版社,1997年2月,第1版:452.
[64] 周柱亮,汪建国,潘涛等.IgA肾病慢性肾衰竭76例临床与病理分析.中国中西医结合肾病杂志,2003:4(1):29.
[65] 郑京,洪江淮,阮诗玮等.IgA肾病病理分级与中医证型关系探讨.福建中医学院学报,2000;10(1):11.
[66] 朱斌,楼季华,俞东蓉.IgA肾病免疫病理和中医辨证的关系.浙江中医学院学报,2001;25(2):35.
[67] 王洪霞.75例IgA肾病的中医辨证分型研究.北京中医杂志,2002;21(1):29.
[68] 汪东丽.IgA肾病的中医辨证论治探讨.河南中医,2004;24(5):52.
[69] 阮诗玮,郑敏麟,王智.IgA肾病的中医辨证研究.中国中医药信息杂志,2000:7(10):43.
[70] 吴竟,邱明山,许琦.IgA肾病湿热证与肾穿刺活检病理组织关系的临床研究,中国中西医结合肾病杂志,2003:4(10):583.
[71] 王海燕.肾脏病学,北京:人民卫生出版社,1997年8月,第2版:717.
[72] 谌贻璞.IgA肾病治疗经验谈.肾脏病与透析肾移植杂志.2002;11(1):42～43.
[73] 刘志红,黎磊石.IgA肾病的分型治疗.肾脏病与透析肾移植杂志,2002:11(1):43～44.
[74] 王力宁,栗霄立.IgA肾病预后判定及治疗.中国实用内科杂志,2003:23(5):258～259.
[75] 张雅君,刘晓渭,陈威等.霉盼酸醋治疗IgA肾病.第四军医大学学报,2003:24