慢性肾小球肾炎（CKD3期）肾络瘀痹证的临床研究
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摘要
目的：探讨慢性肾小球肾炎、慢性肾脏病(CKD)3期肾络瘀痹证的中医证候特点、临床病理表现,以及加味积雪草方、贝那普利及其联用在CKD3期的疗效分析。
方法：1.采用前瞻性、双盲双模拟、随机对照的临床研究方法。2.研究对象：西医诊断为慢性肾小球肾炎(CKD3期)、中医辨证为肾络瘀痹证(瘀痹证)。合并证有肾气阴(血)虚证(肾虚证)、风湿内扰证(风湿证)、湿热内蕴证(湿热证)。3.分析瘀痹证发生率、中医证候特点,以及与蛋白尿、肾功能、肾病理的相关性。4.147例患者分为3组,贝那普利组(西药组)48例、加味积雪草组(中药组)50例、加味积雪草+贝那普利组(中西药组)49例,分析3组治疗前后中医证候、蛋白尿、肾功能等变化。5.统计采用SPSS17.0统计软件分析。
结果：1.慢性肾小球肾炎(CKD3期)肾络瘀痹证发生率69%,并常与肾虚、风湿、湿热等证型同时出现,其中瘀痹肾虚风湿三联证最多见,瘀痹肾虚二联证次之,单独瘀痹证少见。2.瘀痹肾虚二联证在瘀痹证总积分及肌肤甲错积分高于瘀痹肾虚风湿三联证(p<0.05)3.瘀痹证与24小时尿蛋白定量(UPro/24h)有相关性；尿血有不同于其他瘀血证症状特点,其与UPro/24h有相关性(p<0.01)。4.肾病理Andreoli评分提示CKD3期病理急慢性损伤并存,慢性损伤积分重于急性损伤,急性损伤中细胞性新月体比例较高,慢性损伤中节段性硬化比例较高。5.三组治疗后中医证候积分均较治疗前明显下降(p<0.01),中西药组尿血疗效优于西药和中药组(p<0.05)。5.中药组eGFR较治疗前明显升高,较西药组亦升高,但治疗后尿蛋白有增多(p<0.05)。西药组治疗后尿蛋白较中药组减少,差异有统计学差异(p<0.01)。中西药组治疗后较中药组、西药组蛋白尿减少,较西药组eGFR升高(p<0.05)。
结论：1.慢性肾小球肾炎(CKD3期)肾络瘀痹证并不少见,并极大多数与其他证型并存,尤以与虚、风湿三联证多见。2.瘀痹证各症状中以镜下多形性红细胞尿持续存在最具特征,因此在中医辨证中引入尿象检测将有助于提高辩证精准度。3.肾病理Andreoli评分提示CKD3期病理急慢性损伤并存,慢性损伤积分重于急性损伤,急性损伤中细胞性新月体比例较高,慢性损伤中节段性硬化比例较高。4.中药、西药、中西药组均能明显改善慢性肾小球肾炎(CKD3期)肾络瘀痹证中医证候。在尿血治疗中,中西药组能有效减少尿血积分,优于西药和中药组。5.中药组有不依赖于减少尿蛋白的肾保护作用,并能较好改善患者的贫血。6.中西药组(中药与贝那普利的联合治疗)则既能有效减少尿蛋白,又能明显改善肾功能,延缓肾功能衰竭。
Objective:To investigate Traditional Chinese Medical (TCM) characteristics, clinical pathological manifestation of ShenLuoYuBi (YuBi) symptoms in chronic glomerulonephritis (CKD3) patients and effects of jixuecao compounds, benazapril, combined with benazapril and jixuecao compounds.
Methods:A multicenter double blind double dummy randomized controlled clinical study was applied. The patients who were Chronic glomerulonephritis (CKD3stage) had ShenLuoYuBi symptoms with ShenQiYinXu(ShenXu),FengShiNeiRao(FengShi) and ShiReNeiYun(ShiRe) symptoms respectively by syndromes differentiation. The correlations among occurrence rate of ShenLuoYuBi symptom, TCM characteristics, proteinuria, renal function and renal pathological manifestation were analyzed. The147patients were divided into benazapril (48patients), jixuecao compounds (50patients),combined with benazapril and jixuecao compounds groups (49patients). The SPSS17.0was applied.
Results:Occurrence rate of ShenLuoYuBi symptoms in chronic glomerulonephritis (CKD3) patients was69%, accompanied with ShenXu, FengShi and ShiRe symptoms. The patients with two manifestations(YuBi and ShenXu symptoms) had higher scores of YuBi symptoms and squamous and dry skin than the patients with three manifestations (YuBi,ShenXu and FengShi symptoms)(p<0.05). The scores of YuBi symptoms were correlated with UPro/24h. The scores of hematuria which was different from other symptoms of YuBi were also correlated with UPro/24h (p<0.01). According to Andreoli's scores, the patients in CKD3stage both had acute and chronic pathological injury of nephrology, and the scores of chronic pathological injury were higher than the acute injury. Among the acute pathological injury, the number of cellular crescent was greater than others. The scores of segment of glomerular sclerosis were highest in chronic pathological injury. TCM symptom markers in three groups were decreased after treatment (p<0.01). The scores of hematuria had been improved by combined with benazapril and jixuecao compounds treatment while jixuecao compounds or benazapril respectively had no effects (p<0.05). Proteinuria in the patients were increased significantly after treated with jixuecao compounds while e-GFR was raised (p<0.05). The UPro/24h of patients which treated with benazapril reduced effectively than the patients of jixuecao compounds (p<0.01).Proteinuria in the patients treated with benazapril and jixuecao compounds had decreased and renal function had been improved (p<0.05), and the results showed better effect than jixuecao compounds and benazapril treatment respectively.
Conclusion:ShenLuoYuBi symptoms in chronic glomerulonephritis (CKD3) patients are common and accompanied with other TCM symptoms. Hematuria was correlated closely with CKD and would be useful in dialectics of YuBi symptoms in the future. Traditional medicine show renal protective effect independence of lowering proteinuria and improve anemia. Combined with benazapril and traditional medicine show lowering proteinuria and renal protective effect in CKD3patients.
方法：1.采用前瞻性、双盲双模拟、随机对照的临床研究方法。2.研究对象：西医诊断为慢性肾小球肾炎(CKD3期)、中医辨证为肾络瘀痹证(瘀痹证)。合并证有肾气阴(血)虚证(肾虚证)、风湿内扰证(风湿证)、湿热内蕴证(湿热证)。3.分析瘀痹证发生率、中医证候特点,以及与蛋白尿、肾功能、肾病理的相关性。4.147例患者分为3组,贝那普利组(西药组)48例、加味积雪草组(中药组)50例、加味积雪草+贝那普利组(中西药组)49例,分析3组治疗前后中医证候、蛋白尿、肾功能等变化。5.统计采用SPSS17.0统计软件分析。
结果：1.慢性肾小球肾炎(CKD3期)肾络瘀痹证发生率69%,并常与肾虚、风湿、湿热等证型同时出现,其中瘀痹肾虚风湿三联证最多见,瘀痹肾虚二联证次之,单独瘀痹证少见。2.瘀痹肾虚二联证在瘀痹证总积分及肌肤甲错积分高于瘀痹肾虚风湿三联证(p<0.05)3.瘀痹证与24小时尿蛋白定量(UPro/24h)有相关性；尿血有不同于其他瘀血证症状特点,其与UPro/24h有相关性(p<0.01)。4.肾病理Andreoli评分提示CKD3期病理急慢性损伤并存,慢性损伤积分重于急性损伤,急性损伤中细胞性新月体比例较高,慢性损伤中节段性硬化比例较高。5.三组治疗后中医证候积分均较治疗前明显下降(p<0.01),中西药组尿血疗效优于西药和中药组(p<0.05)。5.中药组eGFR较治疗前明显升高,较西药组亦升高,但治疗后尿蛋白有增多(p<0.05)。西药组治疗后尿蛋白较中药组减少,差异有统计学差异(p<0.01)。中西药组治疗后较中药组、西药组蛋白尿减少,较西药组eGFR升高(p<0.05)。
结论：1.慢性肾小球肾炎(CKD3期)肾络瘀痹证并不少见,并极大多数与其他证型并存,尤以与虚、风湿三联证多见。2.瘀痹证各症状中以镜下多形性红细胞尿持续存在最具特征,因此在中医辨证中引入尿象检测将有助于提高辩证精准度。3.肾病理Andreoli评分提示CKD3期病理急慢性损伤并存,慢性损伤积分重于急性损伤,急性损伤中细胞性新月体比例较高,慢性损伤中节段性硬化比例较高。4.中药、西药、中西药组均能明显改善慢性肾小球肾炎(CKD3期)肾络瘀痹证中医证候。在尿血治疗中,中西药组能有效减少尿血积分,优于西药和中药组。5.中药组有不依赖于减少尿蛋白的肾保护作用,并能较好改善患者的贫血。6.中西药组(中药与贝那普利的联合治疗)则既能有效减少尿蛋白,又能明显改善肾功能,延缓肾功能衰竭。
Objective:To investigate Traditional Chinese Medical (TCM) characteristics, clinical pathological manifestation of ShenLuoYuBi (YuBi) symptoms in chronic glomerulonephritis (CKD3) patients and effects of jixuecao compounds, benazapril, combined with benazapril and jixuecao compounds.
Methods:A multicenter double blind double dummy randomized controlled clinical study was applied. The patients who were Chronic glomerulonephritis (CKD3stage) had ShenLuoYuBi symptoms with ShenQiYinXu(ShenXu),FengShiNeiRao(FengShi) and ShiReNeiYun(ShiRe) symptoms respectively by syndromes differentiation. The correlations among occurrence rate of ShenLuoYuBi symptom, TCM characteristics, proteinuria, renal function and renal pathological manifestation were analyzed. The147patients were divided into benazapril (48patients), jixuecao compounds (50patients),combined with benazapril and jixuecao compounds groups (49patients). The SPSS17.0was applied.
Results:Occurrence rate of ShenLuoYuBi symptoms in chronic glomerulonephritis (CKD3) patients was69%, accompanied with ShenXu, FengShi and ShiRe symptoms. The patients with two manifestations(YuBi and ShenXu symptoms) had higher scores of YuBi symptoms and squamous and dry skin than the patients with three manifestations (YuBi,ShenXu and FengShi symptoms)(p<0.05). The scores of YuBi symptoms were correlated with UPro/24h. The scores of hematuria which was different from other symptoms of YuBi were also correlated with UPro/24h (p<0.01). According to Andreoli's scores, the patients in CKD3stage both had acute and chronic pathological injury of nephrology, and the scores of chronic pathological injury were higher than the acute injury. Among the acute pathological injury, the number of cellular crescent was greater than others. The scores of segment of glomerular sclerosis were highest in chronic pathological injury. TCM symptom markers in three groups were decreased after treatment (p<0.01). The scores of hematuria had been improved by combined with benazapril and jixuecao compounds treatment while jixuecao compounds or benazapril respectively had no effects (p<0.05). Proteinuria in the patients were increased significantly after treated with jixuecao compounds while e-GFR was raised (p<0.05). The UPro/24h of patients which treated with benazapril reduced effectively than the patients of jixuecao compounds (p<0.01).Proteinuria in the patients treated with benazapril and jixuecao compounds had decreased and renal function had been improved (p<0.05), and the results showed better effect than jixuecao compounds and benazapril treatment respectively.
Conclusion:ShenLuoYuBi symptoms in chronic glomerulonephritis (CKD3) patients are common and accompanied with other TCM symptoms. Hematuria was correlated closely with CKD and would be useful in dialectics of YuBi symptoms in the future. Traditional medicine show renal protective effect independence of lowering proteinuria and improve anemia. Combined with benazapril and traditional medicine show lowering proteinuria and renal protective effect in CKD3patients.
引文
1.Levey AS,Eckardt KU,Tsukamoto Y,et al.Definition and classification of chronic kidney disease:a position statement from Kidney Disease:Improving Global Outcomes(KDIGO).Kidney Int,2005,67:2089-2100.
2.The international Federation of Kidney Foundations(IFKF)and the internaional Society of Nephrology(ISN),Committee for World Kidney Day.World Kidney Day:an idea whose time has come.http://www.ifkf.com/worldkidneyday.php.
3.张路霞,左力,徐国宾,等.北京市石景山地区中老年人群中慢性肾脏病的流行病学研究.中华肾脏病杂志,2006,22：67-71.
4.吉勤,杨蕊娇.活血化瘀法治疗慢性肾脏病概况.云南中医中药杂志,2009,30(9)：71-72.
5.K/DOQI clinical practice guidelines for chronic kidney disease: evaluation,classification,and stratification.Am J Kidney Dis,2002,39(2 Suppl 1):S1-266.
6.Andreoli SP, Bergstein JM. Treatment of severe IgA nephropathy n children. Pediatr Nephrol.1989 Jul;3(3):248-53.
7.武士锋,王自敏.王自敏从“瘀”论治慢性肾脏病经验.上海中医药杂志,2010,44(6)：19-20.
8.血瘀证诊断参考标准[J].中国中西医结合杂志,1989,(02)：111.
9.刘红,丁小强,徐夏莲,等.慢性肾脏病3～5期伴重度蛋白尿患者的临床病理和预后分析.复旦学报(医学版),2010,37(6)：666-670.
10.王永钧.IgA肾病的中医微观辨证.中国中西医结合肾病杂志,2011,12(2)：95-98.
11. Peterson JC,Adler S,Burkart JM,et al.Blood pressure control, proteinuria, and the progression of renal disease.The modification of diet in renal disease study[J].Ann Intern Med,1995,123(10):754-762.
12.李丹,丁洁.蛋白尿加速慢性肾脏病进展的分子机制.北京大学学报(医学版).2010.42(5)：608-611.
13. B.Subhasree,R.Baskaret,R.Laxmi Keerthana,et al.Evaluation of antioxidant potential in selected green leafy vegetables [J]. Food Chemistry,2009,01:029.
14. Li Hongzhong,Gong Xia,Zhang Li,et al.Madecassoside attenuates inflammatory response on collagen-induced arthritis in DBA/1 mice[J].Phytomedicine,2008,11:002.
15.谢举临,利天增,祈少海,等.积雪草甙对体外培养的成纤维细胞的作用[J].中山医科大学学报,2001,22(1)：41-43.
16.窦晨辉,万毅刚,孙伟,等.中药延缓慢性肾脏病进展的机制[J],中国中药杂志,2009,34(8)：939-943.
17.张仕玉,镇东鑫.赵绍琴治疗慢性肾病的经验.光明中医,2007,22(9)：36-37.
18.张佩青,李淑菊.张琪教授对慢性肾衰竭的辩证论治规律研究.中医药信息,2010：27(5)：39-40.
19.郭永红,李晓翠,张宏,等.吕仁和分期辨证论治慢性肾脏病常用16法.北京中医药,2010,29(9)：671-672.
20.王军,程晓霞,朱晓玲,等.复方积雪草合剂对IgA肾病大鼠肾组织炎症因子和ECM表达的影响.中国中西医结合肾病杂志,2008,9(11)：949-952.
21.杨汝春,王永钧,周大为,等.复方积雪草煎剂对单侧输尿管结扎小鼠肾小管间质骨架蛋白α-SMA、vimentin表达的影响.中国临床药理学与治疗学,2006,,11(9)：1021-1025.
22.陈洪宇,王永钧,覃志成,等.IgAl对肾足细胞分泌VEGF、Col-Ⅳ的影响及复方积雪草2号的干预作用.中国中医药科技,2010,17(6)：489-491.
23.朱晓玲,王永钧,张迎华,等.积雪草甙合大黄素对肿瘤坏死因子a诱导的肾系膜细胞C3表达的影响.中国临床药理学与治疗学,2006,,11(4)：414-417.
24.杜卫华,朱红.下瘀血汤治疗早期肝硬化.吉林中医药,2010,30(4)：336.
25.钦丹萍,蒋挺英,韩建新,等.下瘀血汤防治肝硬化的实验研究[J].中国实验方剂学杂志,1999,5(6)：19-21.
26.钦丹萍,蒋挺英,任永葆,等.下瘀血汤对实验性肝硬化及其脂质过氧化反应干预研究[J].中国中医药信息杂志,2003,10(3)：25-27.
27.慕永平,刘平,刘莺,等.下瘀血汤对进展期大鼠肝纤维化的抑制作用及其方证探讨[J].中医杂志,2006,47(3)：215-218.
28.李慧.下瘀血汤治疗肾络瘀阻型慢性肾炎58例[J].中国医药学报,1997,12(4)：33-34.
29.柴可夫,李慧,楼基伟,等.下瘀血汤对慢性肾功能衰竭大鼠肾组织PCNA阳性细胞、Ⅳ型胶原及FN变化的影响.中国中医药科技,2003,10(3)：140-141.
30.柴可夫,李慧,楼基伟,等.下瘀血汤对5/6肾切除大鼠肾功能的影响.中国医药学报,2003,18(10)：597-600.
1邹万忠.肾活检病理诊断图鉴.北京：人民卫生出版社,2001：6.
2李岩,赵雁,黄启福,等.中医络病的现代认识,北京中医药大学学报,2002,25(3)：1-5.
3中川雅夫.肾小球肾炎、肾病综合征的凝血-纤溶系统异常.日本医学介绍[J].1985,6(8)：366-367.
4雷燕,黄启福,王永炎.论痰毒阻络是络病形成的病理基础[J].北京中医药大学学报,1999,2(2)：8-10.
5王永钧,周柳沙.进一步提高慢性肾脏病的辩证水平.中国中西医结合肾病杂志,2010,11(2)：95-97.
6刘彤宇,韩履祺.于家菊教授运用活血化瘀法治疗肾脏病的经验.中国中西医结合肾病杂志,2007,8(4)：190-191.
7朱世增.邹云翔论肾病.上海：上海中医药大学出版社,2008：60-67.
8吕宏生,彭勃.一代名医吕承全.河南中医学院学报,2005,20(4)：8-12.
9张佩青,李淑菊,王今朝.张琪教授病证结合治疗慢性肾衰竭经验撷菁.新中医,2011,43(8)：171-173.
10陈国姿,田锦鹰.叶任高教授从“瘀”论治肾病的学术思想.中华中医药学刊,2008,26(8)：1747-1748.
11彭建中.赵绍琴教授辨治慢性肾病的学术经验.北京中医药大学学报,1994,17(5)：39-41.
12米秀华.叶景华平衡法思想在慢性肾脏病治疗中的应用.上海中医药杂志,2011,45(4)：3-5.
13蒋燕.王绵之赵绍琴治疗慢性肾功能衰竭的用药经验比较.辽宁中医杂志,2004,31(4)：267-268.
14孙万森.刘锐治疗慢性肾衰心法.陕西中医,1999,20(3)：120-121.
15武士锋.王自敏从“瘀”论治慢性肾脏病经验.上海中医药杂志,2010,44(6)：19-20.
16许筠.刘宝厚教授论治肾病临证经验摘萃.中国中西医结合肾病杂志.2008,9(4)：285-287.
17郭永红,李晓翠,张宏.吕仁和分期辩证论治慢性肾脏病常用16法.北京中医药,2010,29(9)：671-672.
18李靖.吕仁和教授对“肾络癥瘕说”的认识及分期辨治隐匿性肾炎.中国中西医结合肾病杂志,2009,10(8)：661-663.
19邱模炎,李葆青,王绍华.赵绍琴教授基本经验方延缓慢性肾衰竭进展的初步实验研究.中国中西医结合肾病杂志,2007,8(2)：108-109.
20张仕玉,镇东鑫.赵绍琴治疗慢性肾病的经验.光明中医,2007,22(9)：36-37.
21朱雪萍.水道之血宜利,不可轻用止涩-叶景华诊治尿血证的经验.上海中医药杂志,1996,6：12-13.
22郭建文,陈煜辉,兰智慧,等.张琪对王清任学术思想的临床应用与创新.上海中医药杂志,2011,45(7)：4-6.
23余江毅,熊宁宁,余承惠.慢性肾病瘀血与湿热病理的临床和实验研究.辽宁中医杂志,1995,22(2)：91-92.
24张勉之,张大宁.补肾活血法结合西药治疗肾功能衰竭临床观察[J].上海中医药杂志,2004,38(5)：28-30.
25柳丛,饶向荣,李秀英,等.78例慢性肾脏病患者血瘀证与肾小管-间质病理损伤的相关性分析.中国中西医结合肾病杂志,2008,9(3)：251-253.
26胡仲仪,唐利群,陈以平,等.益气活血系列方队膜性肾炎模型基底膜影响的实验研究.中国中西医结合杂志,1999,19(2)：96-99.
27王怡,何立群,郑平东,等.抗纤灵冲剂治疗慢性肾功能衰竭60例疗效研究[J].中医杂志,2003,12(44)：925-927.
28张新志,吴锋,黄迪,等.抗纤灵冲剂对单侧输尿管梗阻模型大鼠肾功能的影响.时珍国医国药,2010,21(10)：2451-2453.
29刘克剑,张悦,李靖,等.抗纤灵方对大鼠单侧输尿管梗阻所致肾纤维化的防治作用.上海中医药大学学报,2009,23(5)：44-47.
30柴可夫,李慧,楼基伟,等.下瘀血汤对慢性肾功能衰竭大鼠肾组织PCNA阳性细胞、Ⅳ型胶原及FN变化的影响.中国中医药科技,2003,10(3)：140-141.
31黎磊石,刘志红,张景红,等.大黄延缓慢性肾衰的临床及实验研究[J].中西医结合杂志,1991,11：392.
32姚健,黎磊石,周红.大黄素对培养人系膜细胞纤维连接蛋白产出的抑制作用[J].肾脏病与透析肾移植杂志,1994,3(5)：349-352.
33何东元,王笑云,王宁宁,等.大黄酸抑制肾成纤维细胞激活的试验研究[J].中华肾脏病杂志,2006,22(2)：105-108.
34宁英远,王俭勤,屈遂林.大黄素对人肾成纤维细胞增殖的影响.中国中西医结合杂志,2000,20(2)：105-106.
35王平,李春雨,沈晓飞,等.大黄水煎液治疗慢性肾功能衰竭的实验研究[J].中药药理与研究,2010,26(5)：91-94.
36闫灵芝,燕浩,孙林成.丹参酮Ⅱa磺酸钠对70例CKD患者肾小球滤过率及肾功能血流阻力指数的影响.求医问药,2011,9(8)：215.
37胡英,查艳,颜晓勇.丹参多酚酸盐治疗早期慢性肾衰竭及对血浆ET-1和CGRP水平的影响.贵州医药,2011,35(6)：502-504.
38陆海英,张悦,刘煜敏,等.丹参酚酸B对肾纤维化大鼠肾组织MMP-2表达的影响.上海中医药大学学报,2009,23(2)：55-58.
39丁红,杨琦,王宗谦,等.丹参酮ⅡA磺酸钠对小鼠肾间质纤维化及CTGF的影响.免疫学杂志,2011,27(5)：398-400.
40徐红.川芎嗪在治疗慢性肾功能衰竭中的作用.中医杂志,2010,51(6)：165-166.
41郑妮军,黄小妹,张英,等.川芎嗪对慢性肾衰竭大鼠TGF-β表达的影响.湖北中医杂志,2008,30(7)：11-12.
42林崇亭,吴达改.红花黄色素治疗慢性肾功能不全的临床分析.中国临床医生,2011,39(1)：48-49.
43孙时华,严富华,姜建军,等.红花黄色素对单侧输尿管梗阻大鼠模型肾间质纤维化的影响.中华中医药学刊,2010,28(4)：891-893.
44王鸿泰,李秀珍,李捷.姜黄对慢性肾衰竭微炎症状态下肾功能的影响.中国中西医结合肾病杂志,2007,8(7)：422-423.
45张俊,刘晓城,周文祥,等.姜黄素对大鼠肾系膜细胞结缔组织生长因子表达的影响.华中科技大学学报(医学版),2006,35(1)：99-102.
46张彬,王全胜,朱锐,等.姜黄素对单侧输尿管梗阻后肾间质纤维化的调节.贵阳医学院学报,2008,33(3)：255-258.
2.The international Federation of Kidney Foundations(IFKF)and the internaional Society of Nephrology(ISN),Committee for World Kidney Day.World Kidney Day:an idea whose time has come.http://www.ifkf.com/worldkidneyday.php.
3.张路霞,左力,徐国宾,等.北京市石景山地区中老年人群中慢性肾脏病的流行病学研究.中华肾脏病杂志,2006,22：67-71.
4.吉勤,杨蕊娇.活血化瘀法治疗慢性肾脏病概况.云南中医中药杂志,2009,30(9)：71-72.
5.K/DOQI clinical practice guidelines for chronic kidney disease: evaluation,classification,and stratification.Am J Kidney Dis,2002,39(2 Suppl 1):S1-266.
6.Andreoli SP, Bergstein JM. Treatment of severe IgA nephropathy n children. Pediatr Nephrol.1989 Jul;3(3):248-53.
7.武士锋,王自敏.王自敏从“瘀”论治慢性肾脏病经验.上海中医药杂志,2010,44(6)：19-20.
8.血瘀证诊断参考标准[J].中国中西医结合杂志,1989,(02)：111.
9.刘红,丁小强,徐夏莲,等.慢性肾脏病3～5期伴重度蛋白尿患者的临床病理和预后分析.复旦学报(医学版),2010,37(6)：666-670.
10.王永钧.IgA肾病的中医微观辨证.中国中西医结合肾病杂志,2011,12(2)：95-98.
11. Peterson JC,Adler S,Burkart JM,et al.Blood pressure control, proteinuria, and the progression of renal disease.The modification of diet in renal disease study[J].Ann Intern Med,1995,123(10):754-762.
12.李丹,丁洁.蛋白尿加速慢性肾脏病进展的分子机制.北京大学学报(医学版).2010.42(5)：608-611.
13. B.Subhasree,R.Baskaret,R.Laxmi Keerthana,et al.Evaluation of antioxidant potential in selected green leafy vegetables [J]. Food Chemistry,2009,01:029.
14. Li Hongzhong,Gong Xia,Zhang Li,et al.Madecassoside attenuates inflammatory response on collagen-induced arthritis in DBA/1 mice[J].Phytomedicine,2008,11:002.
15.谢举临,利天增,祈少海,等.积雪草甙对体外培养的成纤维细胞的作用[J].中山医科大学学报,2001,22(1)：41-43.
16.窦晨辉,万毅刚,孙伟,等.中药延缓慢性肾脏病进展的机制[J],中国中药杂志,2009,34(8)：939-943.
17.张仕玉,镇东鑫.赵绍琴治疗慢性肾病的经验.光明中医,2007,22(9)：36-37.
18.张佩青,李淑菊.张琪教授对慢性肾衰竭的辩证论治规律研究.中医药信息,2010：27(5)：39-40.
19.郭永红,李晓翠,张宏,等.吕仁和分期辨证论治慢性肾脏病常用16法.北京中医药,2010,29(9)：671-672.
20.王军,程晓霞,朱晓玲,等.复方积雪草合剂对IgA肾病大鼠肾组织炎症因子和ECM表达的影响.中国中西医结合肾病杂志,2008,9(11)：949-952.
21.杨汝春,王永钧,周大为,等.复方积雪草煎剂对单侧输尿管结扎小鼠肾小管间质骨架蛋白α-SMA、vimentin表达的影响.中国临床药理学与治疗学,2006,,11(9)：1021-1025.
22.陈洪宇,王永钧,覃志成,等.IgAl对肾足细胞分泌VEGF、Col-Ⅳ的影响及复方积雪草2号的干预作用.中国中医药科技,2010,17(6)：489-491.
23.朱晓玲,王永钧,张迎华,等.积雪草甙合大黄素对肿瘤坏死因子a诱导的肾系膜细胞C3表达的影响.中国临床药理学与治疗学,2006,,11(4)：414-417.
24.杜卫华,朱红.下瘀血汤治疗早期肝硬化.吉林中医药,2010,30(4)：336.
25.钦丹萍,蒋挺英,韩建新,等.下瘀血汤防治肝硬化的实验研究[J].中国实验方剂学杂志,1999,5(6)：19-21.
26.钦丹萍,蒋挺英,任永葆,等.下瘀血汤对实验性肝硬化及其脂质过氧化反应干预研究[J].中国中医药信息杂志,2003,10(3)：25-27.
27.慕永平,刘平,刘莺,等.下瘀血汤对进展期大鼠肝纤维化的抑制作用及其方证探讨[J].中医杂志,2006,47(3)：215-218.
28.李慧.下瘀血汤治疗肾络瘀阻型慢性肾炎58例[J].中国医药学报,1997,12(4)：33-34.
29.柴可夫,李慧,楼基伟,等.下瘀血汤对慢性肾功能衰竭大鼠肾组织PCNA阳性细胞、Ⅳ型胶原及FN变化的影响.中国中医药科技,2003,10(3)：140-141.
30.柴可夫,李慧,楼基伟,等.下瘀血汤对5/6肾切除大鼠肾功能的影响.中国医药学报,2003,18(10)：597-600.
1邹万忠.肾活检病理诊断图鉴.北京：人民卫生出版社,2001：6.
2李岩,赵雁,黄启福,等.中医络病的现代认识,北京中医药大学学报,2002,25(3)：1-5.
3中川雅夫.肾小球肾炎、肾病综合征的凝血-纤溶系统异常.日本医学介绍[J].1985,6(8)：366-367.
4雷燕,黄启福,王永炎.论痰毒阻络是络病形成的病理基础[J].北京中医药大学学报,1999,2(2)：8-10.
5王永钧,周柳沙.进一步提高慢性肾脏病的辩证水平.中国中西医结合肾病杂志,2010,11(2)：95-97.
6刘彤宇,韩履祺.于家菊教授运用活血化瘀法治疗肾脏病的经验.中国中西医结合肾病杂志,2007,8(4)：190-191.
7朱世增.邹云翔论肾病.上海：上海中医药大学出版社,2008：60-67.
8吕宏生,彭勃.一代名医吕承全.河南中医学院学报,2005,20(4)：8-12.
9张佩青,李淑菊,王今朝.张琪教授病证结合治疗慢性肾衰竭经验撷菁.新中医,2011,43(8)：171-173.
10陈国姿,田锦鹰.叶任高教授从“瘀”论治肾病的学术思想.中华中医药学刊,2008,26(8)：1747-1748.
11彭建中.赵绍琴教授辨治慢性肾病的学术经验.北京中医药大学学报,1994,17(5)：39-41.
12米秀华.叶景华平衡法思想在慢性肾脏病治疗中的应用.上海中医药杂志,2011,45(4)：3-5.
13蒋燕.王绵之赵绍琴治疗慢性肾功能衰竭的用药经验比较.辽宁中医杂志,2004,31(4)：267-268.
14孙万森.刘锐治疗慢性肾衰心法.陕西中医,1999,20(3)：120-121.
15武士锋.王自敏从“瘀”论治慢性肾脏病经验.上海中医药杂志,2010,44(6)：19-20.
16许筠.刘宝厚教授论治肾病临证经验摘萃.中国中西医结合肾病杂志.2008,9(4)：285-287.
17郭永红,李晓翠,张宏.吕仁和分期辩证论治慢性肾脏病常用16法.北京中医药,2010,29(9)：671-672.
18李靖.吕仁和教授对“肾络癥瘕说”的认识及分期辨治隐匿性肾炎.中国中西医结合肾病杂志,2009,10(8)：661-663.
19邱模炎,李葆青,王绍华.赵绍琴教授基本经验方延缓慢性肾衰竭进展的初步实验研究.中国中西医结合肾病杂志,2007,8(2)：108-109.
20张仕玉,镇东鑫.赵绍琴治疗慢性肾病的经验.光明中医,2007,22(9)：36-37.
21朱雪萍.水道之血宜利,不可轻用止涩-叶景华诊治尿血证的经验.上海中医药杂志,1996,6：12-13.
22郭建文,陈煜辉,兰智慧,等.张琪对王清任学术思想的临床应用与创新.上海中医药杂志,2011,45(7)：4-6.
23余江毅,熊宁宁,余承惠.慢性肾病瘀血与湿热病理的临床和实验研究.辽宁中医杂志,1995,22(2)：91-92.
24张勉之,张大宁.补肾活血法结合西药治疗肾功能衰竭临床观察[J].上海中医药杂志,2004,38(5)：28-30.
25柳丛,饶向荣,李秀英,等.78例慢性肾脏病患者血瘀证与肾小管-间质病理损伤的相关性分析.中国中西医结合肾病杂志,2008,9(3)：251-253.
26胡仲仪,唐利群,陈以平,等.益气活血系列方队膜性肾炎模型基底膜影响的实验研究.中国中西医结合杂志,1999,19(2)：96-99.
27王怡,何立群,郑平东,等.抗纤灵冲剂治疗慢性肾功能衰竭60例疗效研究[J].中医杂志,2003,12(44)：925-927.
28张新志,吴锋,黄迪,等.抗纤灵冲剂对单侧输尿管梗阻模型大鼠肾功能的影响.时珍国医国药,2010,21(10)：2451-2453.
29刘克剑,张悦,李靖,等.抗纤灵方对大鼠单侧输尿管梗阻所致肾纤维化的防治作用.上海中医药大学学报,2009,23(5)：44-47.
30柴可夫,李慧,楼基伟,等.下瘀血汤对慢性肾功能衰竭大鼠肾组织PCNA阳性细胞、Ⅳ型胶原及FN变化的影响.中国中医药科技,2003,10(3)：140-141.
31黎磊石,刘志红,张景红,等.大黄延缓慢性肾衰的临床及实验研究[J].中西医结合杂志,1991,11：392.
32姚健,黎磊石,周红.大黄素对培养人系膜细胞纤维连接蛋白产出的抑制作用[J].肾脏病与透析肾移植杂志,1994,3(5)：349-352.
33何东元,王笑云,王宁宁,等.大黄酸抑制肾成纤维细胞激活的试验研究[J].中华肾脏病杂志,2006,22(2)：105-108.
34宁英远,王俭勤,屈遂林.大黄素对人肾成纤维细胞增殖的影响.中国中西医结合杂志,2000,20(2)：105-106.
35王平,李春雨,沈晓飞,等.大黄水煎液治疗慢性肾功能衰竭的实验研究[J].中药药理与研究,2010,26(5)：91-94.
36闫灵芝,燕浩,孙林成.丹参酮Ⅱa磺酸钠对70例CKD患者肾小球滤过率及肾功能血流阻力指数的影响.求医问药,2011,9(8)：215.
37胡英,查艳,颜晓勇.丹参多酚酸盐治疗早期慢性肾衰竭及对血浆ET-1和CGRP水平的影响.贵州医药,2011,35(6)：502-504.
38陆海英,张悦,刘煜敏,等.丹参酚酸B对肾纤维化大鼠肾组织MMP-2表达的影响.上海中医药大学学报,2009,23(2)：55-58.
39丁红,杨琦,王宗谦,等.丹参酮ⅡA磺酸钠对小鼠肾间质纤维化及CTGF的影响.免疫学杂志,2011,27(5)：398-400.
40徐红.川芎嗪在治疗慢性肾功能衰竭中的作用.中医杂志,2010,51(6)：165-166.
41郑妮军,黄小妹,张英,等.川芎嗪对慢性肾衰竭大鼠TGF-β表达的影响.湖北中医杂志,2008,30(7)：11-12.
42林崇亭,吴达改.红花黄色素治疗慢性肾功能不全的临床分析.中国临床医生,2011,39(1)：48-49.
43孙时华,严富华,姜建军,等.红花黄色素对单侧输尿管梗阻大鼠模型肾间质纤维化的影响.中华中医药学刊,2010,28(4)：891-893.
44王鸿泰,李秀珍,李捷.姜黄对慢性肾衰竭微炎症状态下肾功能的影响.中国中西医结合肾病杂志,2007,8(7)：422-423.
45张俊,刘晓城,周文祥,等.姜黄素对大鼠肾系膜细胞结缔组织生长因子表达的影响.华中科技大学学报(医学版),2006,35(1)：99-102.
46张彬,王全胜,朱锐,等.姜黄素对单侧输尿管梗阻后肾间质纤维化的调节.贵阳医学院学报,2008,33(3)：255-258.