用户名: 密码: 验证码:
糖尿病肾病中医证型与TWEAK等炎症因子相关性研究
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
目的
     1、观察糖尿病肾病患者中医证候特点。
     2、探讨糖尿病肾病患者各中医证型与临床分期及相关理化指标的相关性。
     3、观察糖尿病肾病患者炎症指标的变化特征。
     4、观察TWEAK在糖尿病肾病中的表达变化,探讨糖尿病肾病、中医证型与炎症之间的关系。
     方法
     1、临床研究
     回顾性分析2012年9月-2013年3月广州中医药大学附属深圳市中医院和宝安区中医院的糖尿病肾病152名,通过建立数据库,整理分析患者的临床证型、理化指标等,并依据2007年中华中医药学会肾病分会制定的《糖尿病肾病诊断、辨证分型及疗效评定标准》和《Mogensen糖尿病肾脏分期标准》,分别对所收集的糖尿病肾病病例进行中医辨证及西医诊断分期,应用SPSS统计软件,分析糖尿病肾病患者中医证型与西医理化指标、临床资料、糖尿病肾病分期的相关性。
     2、实验研究
     利用酶联免疫吸附剂测定法(ELISA),检测所纳入的120名糖尿病肾病和30名健康组患者的血、尿TWEAK,血IL-1β及血IL-10等相关炎症指标,对比分析各中医证型间各炎症因子浓度差异,分析糖尿病肾病患者血、尿TWEAK,血IL-1β及血IL-10与中医辨证分型的相关性。
     结果
     1、临床研究
     (1)糖尿病分期方面:频数分析结果提示152例糖尿病肾病患者,中医本证包括气阴两虚证最多见100例(65.79%),阴虚燥热证6例(3.94%),脾肾气虚证24例(15.79%),阴阳两虚证22例(14.47%),共152例;标证中湿热证16例(10.53%),寒湿证共34例(22.37%),瘀证共52例(34.21%),痰瘀证共8例(5.26%)。结合糖尿病肾病的西医临床分期:主证中阴虚燥热证Ⅰ-Ⅱ期2例,Ⅲ期2例,Ⅳ期2例;气阴两虚证Ⅰ-Ⅱ期16例,Ⅲ期30例,Ⅳ期54例;脾肾气虚证Ⅰ-Ⅱ期6例,Ⅲ期8例,Ⅳ期10例;阴阳两虚证Ⅰ-Ⅱ期4例,Ⅲ期4例,Ⅳ期12例,V期2例;标证中湿热证Ⅰ-Ⅱ期6例,Ⅲ期2例,Ⅳ期8例;寒湿证Ⅰ-Ⅱ期0例,Ⅲ期10例,Ⅳ期24例;瘀证Ⅰ-Ⅱ期4例,Ⅲ期20例,Ⅳ期28例;痰瘀证Ⅰ-Ⅱ期2例,Ⅲ期0例,Ⅳ期26例。结果提示中医辨证分型与糖尿病肾病分期存在相关性(P<0.05,r=0.522)。
     (2)临床分析:在152例DN患者中,口干多饮及小便频数症状在中医多个证型(包括本证及标证)中是成对出现,其中阴虚燥热证4例(2.6%),气阴两虚证46例(30.3%),脾肾气虚证8例(5.2%),阴阳两虚证8例(5.2%),湿热证4例(2.6%),寒湿证16例(10.5%),瘀证8例(5.2%),痰瘀证8例(5.2%),而多食易饥在糖尿病肾病患者当中表现较少,阴虚燥热证2例(1.3%),气阴两虚证4例(2.6%),阴阳两虚证2例(1.3%)。结果提示中医辨证分型与糖尿病主要症状存在相关性(P<0.05,r=0.415)。
     (3)并发症分析:在152例DN患者中,中医各个证型本证当中,冠心病(心电图改变)最多见52例(34.2%),然后依次是脑血管意外32例(21.1%),视网膜病变28例(18.4%),周围神经病变17例(11.2%),标证当中仍以冠心病(心电图改变)最多见40例(26.3%),然后依次是脑血管意外32例(21.1%),视网膜病变19例(12.5%),周围神经病变19例(12.5%)。结果提示中医辨证分型与糖尿病肾病并发症存在相关性(P<0.05,r=0.383)。
     (4)理化指标分析:本研究结果显示:空腹胰岛素(INS),糖化血红蛋白(HbAlc),体重指数(BMI),尿蛋白(Upro),尿肌酐(Ucr),尿蛋白肌酐比值(Upro/Ucr),红细胞计数(RBC),肝功能(AST、ALB)、血脂(TG、LDL-C、 HDL-C)、甲状腺功能(FT3、FT4、TSH),肿瘤三项(CA199、AFP、CEA2)组各证比较无统计学差异(P>0.05)。
     各组间差异显著的理化指标包括空腹血糖(FPG)、谷丙转氨酶(ALT)、血肌酐(Cr)、胱抑素C (Cys-C)、血总胆固醇(CHOL)、血红蛋白(HGB)等。其中,空腹血糖:脾肾气虚证与阴虚燥热证、湿热证、气阴两虚证有统计学差异(P<0.05),痰瘀证与其它各证型之间比较均有统计学差异(P<0.05);血清谷丙转氨酶:寒湿证组最高,与各证均有统计学差异(P<0.05),阴虚燥热证及气阴两虚证数值也明显增高,与其它各证比较有统计学差异(P<0.05),阴虚燥热证与气阴两虚证比较无统计学差异(P>0.05);血肌酐:阴阳两虚证明显高于其它组,与阴虚燥热证、瘀证比较有统计学差异(P<0.05),而阴虚燥热证明显低于其它组,与气阴两虚证、瘀证比较有统计学差异(P<0.05);胱抑素C:阴阳两虚证也明显高于其它组;血总胆固醇:瘀证明显高于其它组,与非气阴两虚证、阴阳两虚证比较有统计学差异(P<0.05),气阴两虚证与脾肾气虚、湿热证比较有统计学差异(P<0.05);红细胞计数:阴阳两虚证明显低于其它组,组间对比虽然差异无统计学意义,但是降低比较明显;血红蛋白:阴阳两虚证明显低于其它组,且与各证比较有统计学差异(P<0.05),阴虚燥热证明显高于其它组,与各证比较有统计学差异(P<0.05),气阴两虚证与非痰瘀证比较有统计学差异(P<0.05),痰瘀证与非气阴两虚证比较有统计学差异(P<0.05);上述结果提示中医证型与FPG、 RBC、 HGB、 CHOL、 ALT、 Cr和Cys-C水平可能有关。
     2、实验研究
     实验结果显示:主证中:血、尿TWEAK,血IL-10浓度水平随中医证型病情进展逐步降低,其中阴虚燥热证组血、尿TWEAK,血IL-I0浓度明显高于其它组,与其它证型对比差异有统计学意义(P<0.05),按浓度排序依次为:阴虚燥热证>气阴两虚证>脾肾气虚证、阴阳两虚证,与健康组和糖尿病肾病病情进展(无蛋白尿组、少量蛋白尿组、大量蛋白尿组、肾功能不全组)表达水平一致;血清IL-1β检测结果提示:与正常对照组和其他证型组比较,湿热证组IL-1β浓度较高,差别具有统计学意义(P<0.05)。
     结论
     1、结果提示中医辨证分型与糖尿病肾病分期的相关性有统计学意义(P<0.05),具有相关性,说明伴随着患者糖尿病肾病病情加重,中医证型从阴虚燥热→气阴两虚→脾肾气虚→阴阳两虚证发展,中医证型发展也是病情加重的一个反映。中医辨证分型(包括本证和标证)与临床表现及并发症的相关性有统计学意义(P<0.05),我们认为糖尿病“三多一少”症及并发症在糖尿病肾病的中医辨证中可以做为衡量病情严重程度的指标。
     2、糖尿病肾病的中医证型与理化指标FPG、HGB、CHOL、CREA和Cys-C差别有统计学意义,存在相关性。
     3、各中医证型间的血、尿TWEAK.血IL-1β、血IL-10浓度存在差异,提示中医分型与此类血、尿炎症因子的表达分泌有关。提示湿热证、阴虚燥热证可能与炎症关系密切。利用炎症因子有望对中医证型的发生机制进行阐释。
Objecti ve
     1、 To observe the TCM syndromes characteristics in patients with diabetic nephropathy(DN).
     2、 To explore the correlation between TCM syndromes、 different stages and physicochemical index in patients with DN.
     3、 To observe the change of inflammatory markers in patients with DN.
     4、 To observe the expression change of TWEAK in diabetic DN, to explore the relationship between diabetic nephropathy and inflammation
     Methods
     1、 Clinical studies
     We have done retrospective analysis of152patients with DN from Shenzhen TCM Hospital and Baoan District TCM Hospital of Subsidiary TCM University of Guangzhou during2012.09-2013.03. Through the establishment of a database, analysis of DN stages clinical syndromes, physicochemical index. According to the2007China Association of Chinese medicine nephropathy branch had made the 《diabetic nephropathy diagnosis, syndrome differentiation and therapeutic effect evaluation standard》and《Mogensen diabetic kidney staging criteria》, The152patients were carried out TCM syndromes and Western medicine diagnosis staging, and then used SPSS statistical software to analyse the relationship between TCM types and physicochemical index、 DN stages、 clinical data of patients with diabetic nephropathy.
     2、 Experimental Study
     To study serum、urine inflammatory factors:TWEAK、IL-1β and IL-10by using Experimental study of enzyme linked immunosorbent assay (ELISA) method on120diabetic nephropathy patients and normal persons, and analyses the correlation between patients with diabetic nephropathy and normal human serum and urine concentration and diabetic nephropathy
     syndromes of TCM.
     Results
     1、 Clinical studies
     The study selected152cases according to the general condition of patients, symptoms, signs, physicochemical index and diabetic nephropathy stage were compared and analysed the correlation of TCM types and clinical data、 physicochemical index, diabetic nephropathy stage, as follows:
     (1) General data analysis:152cases of patients with diabetic nephropathy,77cases were male,34to81years of age, mean age was64.64±12.56years old, average disease course was11.56±5.38years;75cases were female, aged38years to84years, mean age was63.55±10.94years, average disease course was10.16±6.36months.
     (2) The distribution of TCM types:The frequency analysis showed that:Qi-Yin deficiency was the major type,100cases (65.79%), yin deficiency dryness-heat was6cases (3.94%), Qi deficiency of spleen and kidney was24cases (15.79%), yin-yang deficiency was22cases (14.47%), cold-dampness、 Damp-heat、 blood stasis、 Phlegm and blood stasis, respectively was16cases (10.53%)、34cases (22.37%)、8cases (34.21%) and8cases (5.26%). In yin deficiency dryness-heat of the main type, there were2cases was Ⅰ-Ⅱ stage,2cases was Ⅲstage,2cases was Ⅳ stage; In Qi-Yin deficiency, there were16cases was Ⅰ-Ⅱ stage,30cases was Ⅲ stage,54cases was Ⅳ stage; In Qi deficiency of spleen and kidney, there were6cases was Ⅰ-Ⅱ stage,8cases was Ⅲstage,10cases was Ⅳ stage; In yin-yang deficiency, there were4cases was Ⅰ-Ⅱ stage,4cases was Ⅲstage,12cases was Ⅳ stage; In Damp-heat type of the concurrently type, Ⅰ-Ⅱ stage, Ⅲstage, and Ⅳstage were respectively6cases,2cases,8cases. In cold-dampness type of the concurrently type, Ⅰ-Ⅱ stage, Ⅲ stage, and Ⅳstage were respectively0cases,10cases,24cases. In blood stasis type of the concurrently type, Ⅰ-Ⅱ stage, Ⅲstage, and Ⅳstage were respectively4cases,20cases,28cases. In Phlegm and blood stasis type of the concurrently type,Ⅰ-Ⅱ stage, Ⅲstage, and Ⅳstage were respectively2cases,0cases,26cases.
     (3) The Clinical syndromes:The frequency analysis showed that:Dry mouth polydipsia and frequent urination symptom in TCM Different Syndromes (including the main and concurrently syndromes) which appear in pairs, there was4cases(2.6%) in yin deficiency dryness-heat; Qi-Yin ficiency were46cases (30.3%), Qi deficiency of spleen and kidney were8cases (5.2%), yin-yang deficiency were8cases (5.2%), cold-dampness. Damp-heat、 blood stasis. Phlegm and blood stasis, respectively was4cases (2.6%)、16cases (10.5%)、8cases (5.26%) and8cases (5.26%).
     (4)152cases of patients with diabetic nephropathy:In the main syndromes of all TCM Syndromes, The coronary disease,52cases (34.2%) was the major type, strokes was32cases (21.1%), retina disease was28cases (18.4%), round neuropathy was17cases (11.2%), Samely, In the concurrently type The coronary disease,40cases (26.3%) was also the major type, then the strokes, retina disease, round neuropathy were respectively32cases (21.1%),19cases (12.5%),19cases (12.5%)。
     (5) Physicochemical indicators:Physicochemical indicators:The results showed that physicochemical indexes of INS, HbAlc, BMI, RBC, Upro, Ucr, Upro/Ucr, AST, ALB, TG, LDL-C, HDL-C、 FT3, FT4, TSH, CA199, AFP and CEA2in groups of differential TCM types have no difference (P>0.05)。
     Physicochemical indicators of a significant difference between groups including fasting blood glucose (FPG), alanine aminotransferase (ALT), serum creatinine (Cr), Cystatin C (Cys-C), serum total cholesterol (CHOL), hemoglobin (HGB) etc. The FPG of Qi deficiency of spleen and kidney type was significantly lower than yin deficiency dryness-heat. Damp-heat and kidney and Qi-Yin deficiency (P<0.05), Phlegm and blood stasis was significantly lower than the other types (P<0.05); The ALT of cold-dampness type was significantly higher than the other types (P<0.05), Yin deficiency dryness-heat and Qi-Yin deficiency higher than the other syndromes (P<0.05), but no cold-dampness type (P<0.05); but the two types have no difference (P>0.05); The CREA of yin-yang deficiency type was significantly higher than yin deficiency dryness-heat and blood stasis (P<0.05), Yin deficiency dryness-hea was significantly lower than Qi-Yin deficiency and blood stasis types (P<0.05); The CREA of blood stasis type was significantly higher than the other syndromes, but no Qi-Yin deficiency and yin-yang deficiency (P<0.05), Qi-Yin deficiency syndromes was significantly lower than Qi deficiency of spleen and kidney and Damp-heat types; The HGB of yin-yang deficiency type was significantly lower than the other syndromes (P<0.05), It has significantly difference between Qi-Yin deficiency and no Phlegm and blood stasis (P<0.05), It has significantly difference between Phlegm and blood stasis and no Qi-Yin deficiency (P<0.05), These results may suggest that TCM types have relevant with FPG、RBC、 HGB、 CHOL、 CREA and Cys-C.
     2、 Experimental Study
     In the study, The experimental results showed that:The blood and urine TWEAK、 blood IL-β、blood IL-10of yin deficiency dryness-heat of LN patients were significantly higher than the other types (P<0.05), In the main types, The blood and urine TWEAK、blood IL-1β、blood IL-10become lower and lower with the development of TCM types, such as yin deficiency dryness-heat>Qi-Yin deficiency>Qi deficiency of spleen and kidney and yin-yang deficiency, It was same with the development of DN(the normal persons, DN without albumen、 DN with a small amount albumen、 DN with a great amount albumen DN with CRF). Conclusion
     1、 It has correlation between clinical symptoms、 complications DN、 stage and TCM syndromes in patients with DN.
     2、 It has correlation between the TCM syndromes and FPG、 HGB、 CHOL、 Cr、 Cys-C.
     3、 There are some difference of blood and urine TWEAK、 blood IL-β、blood IL-10expressing between normal persons and DN patients, It point out that has correlation between TCM syndromes and secretion expression of these blood、 urine inflammation factors. It has close relationship between Damp-heat type、 yin deficiency dryness-heat and inflammation, we may can use inflammation factors technology to reveal the mechanism of TCM syndromes.
引文
[1]倪青.著名中医学家林兰教授学术经验系列之四:病机以气阴两虚为主治疗当益气养阴为先:治疗糖尿病肾病的经验[J].辽宁中医杂志,2007,27(4):145-146。
    [2]赵迪.高彦彬教授治疗糖尿病肾病学术思想和经验[J].中医研究,2007,20(1):42-44。
    [3]吕仁和,赵进喜,王越.糖尿病肾病临床研究述评[J].北京中医药大学学报,1994,7(2):2-5。
    [4]李秀华,李凤婷,李梦,等.糖尿病肾病中医病名及病因病机浅述[J]安徽中医学院学报第2010,29(6):7-9。
    [5]高彦彬,吕仁和,王秀琴,等.糖肾宁治疗糖尿病肾病的临床研究[J].中医杂志,1997,38(2):96-99。
    [6]吕仁和,时振声.糖尿病肾病的中医诊治.北京中医,1989,2:8-10.
    [7]宋述菊,牟宗秀.糖尿病肾病病因病机及辫治探讨[J].山东中医杂志,1999,18(4):147
    [8]何泽,南征.糖尿病肾病“毒损肾络”中医病机假说探讨[J].医药世界2006,09:11-12
    [9]黄翠玲,李才,邓义斌,等.济肾汤对糖尿病大鼠肾脏病变的影响[J].中国中西医结合杂志,1997,17(1):676。
    [10]李楠,南征.南征教授从毒论治消渴肾病撷粹[J].天津中医药,2008,25(2):94-95.
    [11]朱善勇,龚婕宁.“久病入络”论及其在糖尿病肾病防治中的应用[J].中医药导报,2009,15(11):4-5。
    [12]屠伯言.糖尿病肾病用补肾活血法治疗的临床和实验研究[J].上海中医药杂志,1991,25(1):1-4。
    [13]张振忠,豆小妮,赵宏波,等.参芪糖肾安胶囊治疗糖尿病肾病的动物实验研究[J].现代中医药,2007,27(3):69-71。
    [14]魏连波,陈旭红,马志刚,等.氯沙坦配合加味六味地黄丸对老年糖尿病肾病早期尿微量白蛋白排泄率的影响[J].中国中西医结合肾病杂志,2000,1(2):85-87。
    [15]黄学民,赵进喜.糖尿病肾病的中医分期分型辨证探讨[J].中国老年保健医学,2005,3(1):28-29。
    [16]牟新,姜淼,宋美铃.赵进喜教授治疗糖尿病肾病经验介绍[J].新中医,2005,37(11):15-16。
    [17]李小会,董正华,丁辉.糖尿病肾病病因病机的探讨[J].陕西中医,2005,26(6):552
    [18]贺学林.陈以平教授治疗糖尿病肾病临床经验[J].中国中西医结合肾病杂志,2000,1(1):7-8。
    [19]张岩糖尿病肾病的中医病因病机浅析光明中医2010,25(3):406-407。
    [20]张振忠,豆小妮,赵宏波.糖尿病肾病发病机理的研究进展[J].现代中医药2008,28(2):55-57。
    [21]陈延强,史伟,黄玉茵.糖尿病肾病中医分期辨治的探讨[J].新中医2008,41(3):3-4。
    [22]薛国忠,戴恩来.刘宝厚教授治疗糖尿病肾病经验[J].中国中西医结合肾病杂志,2007,8(6):314-315。
    [23]陈莹莹,李敬林.2型糖尿病炎症学说的中医[J].探讨实用中医内科杂志,2012,26(12):47-48.
    [24]张红敏,谢春光,陈世伟.动脉粥样硬化、2型糖尿病等疾病发病学说中低度炎症的中医病理探讨[J].中医杂志,2005,46(2):83.
    [25]王忆黎,严余明.试述2型糖尿病炎症发病说对中医临床的意义[J].浙江中医学院学报,2003,27(3)
    [26]于淼,朴春丽,南征.从毒损肝络探讨胰岛素抵抗、2型糖尿病炎症发病机制[J].中华实用中西医杂志,2006,19(6):614.
    [27]苑天彤,秦曼,迟继铭.参芪消肾汤对糖尿病肾病大鼠血清CRP及肾组织MCP-I表达的影响[J].中国中西医结合肾病杂志,2009,10(1):49-51.
    [28]朴春丽,杨叔禹,仝小林.解毒通络保肾法抑制糖尿病肾病炎症发病机制的研究[J].实用中西医结合临床,2009,9(3):1-5.
    [29]复旦大学上海医学院,实用内科学编委会,陈灏珠.实用内科学(M).人民卫生出版社,2009:2303-2308。
    [30]余敏,周宏灏,刘昭前.糖尿病肾病相关基因研究进展[J].中国药理学通报,2008,24(11):1419-1422。
    [31]左彦方龙爱梅黄晓青等.血管紧张素转换酶基因多态性与2型糖尿病肾病相关性的Meta分析[J].中国循证医学杂志2012,12(9):1071-1075。
    [32]吴燕,吕红彬,蒋玲等.多元醇通路与糖尿病性视网膜病变的研究进展[J].国际眼科杂志,2009,9(2):335-337。
    [33]Dagher Z, Park YS, AsnaghiV, etal. Studies of ratand human ret-inas predicta role for the polyolpathway in human diabetic retinopathy. Diabetes2004,53(9): 2404-2411.
    [34]冯敏,黄国良糖基化终产物及其受体系统与糖尿病肾病[J].医学综述2009,15(23):3623-3625。
    [35]姚丽,王力宁,周华,等.胰岛素对糖尿病大鼠肾小球蛋白激酶C表达的调控[J].中国现代医学杂志,2003,13(18):7-10。
    [36]齐伟,牟娇,郭艳红,等.蛋白酶体抑制剂对糖尿病肾病大鼠的治疗作用[J].医学研究生学报,2010,23(9):910-914。
    [37]张琳郁.彩色多普勒超声对糖尿病肾病肾脏血流动力学的观察分析[J].中国实用医药2008,3(26):19-20。
    [38]廉永听张嘉莉李兢.糖尿病肾病发病机制研究进展[J].中国疗养医学2012,21(6):515-516。
    [39]吴红花郭晓蕙高妍,等。调脂治疗对OLETF大鼠肾脏的保护作用[J].中国糖尿病杂志.2006,14(1):60-62。
    [40]邓祁清,段顺元,桂庆军,等.2型糖尿病患者尿白蛋白排出量与血脂代谢异常的关系.[J].现代诊断与治疗,2006,17,1001。
    [41]Dubois D, Chanson P, Timsit J, et al. Remission of proteinuria following. Correction of hyperlipidemia in NIDDM patients with nondiabetic glomerulopathy. Diabetes Care,1994,17:906。
    [42]张雯伊,田浩明,梁基忠.2型糖尿病患者血清脂蛋白(a)水平变化及其意义.中华内分泌代谢杂志,1999,15:300。
    [43]孙永新,范愈燕,支楠,等.肾内血管紧张素系统在2型糖尿病大鼠的肾脏发育中异 常活化的机制[J].中国医科大学学报.2012,41(10):865-869。
    [44]Liu BC, Chen L, Sun Jet allConnective tissue growth factor-mediated angiotensin II-induced hypertrophy of proximal tubular cellslNephron Exp Nephro,1 2006; 103: e16-e26。
    [45]侯振江(?)细胞因子在糖尿病肾病中的研究进展[J].医学与哲学(临床决策论坛版),2007,28(7):58-60。
    [46]刘淑贤.糖尿病患者血浆内皮素水平及其与微血管病变的关系[J].临床内科杂志,2005,22(4):268-269。
    [47]张延峰,王桂英.内皮素与糖尿病的关系及临床意义[J].现代预防医学,2005,32(6):696。
    [48]Jaffa AA, Durazo-Arvizu R, Zheng D, et a.1 Plasma prekallikrein:ariskmarker forhypertension and nephropathy in typel diabetes. Dia-betes,2003,52(5):1215-1221。
    [49]刘桂馨,江晓津,张树范,等.糖尿病肾病前列腺素变化与肾脏损害的关系齐鲁医学杂志,1999,14(4):249-251。
    [50]Bank N, Aymed jiam HS. Role EDRE(nitic oxide) in d-iabetic renal hyperfiltration [J]. Kidney Int,1993,43(6):1306-1312.
    [51]Xiao H, Li Y, Qi J, et al. Peroxynitrite plays a keyrole in glomerular lesions in diabetic rats[J].J Neph-rol,2009,22(6):800-808.
    [52]董静,于桂娜。ET/NO、t-PA/PAI-1及TXA2/PGI2与糖尿病肾病的关系[J].山东医药2006,46(16):93-94。
    [53]张城,施丹,刘卫清,等.心房利钠肽在心血管疾病中的研究进展吉林医学2012,33(4):820-822。
    [54]李思佳,指导:刘育军.转化生长因子β对糖尿病肾病作用研究进展[J].辽宁中医药大学学报,2011,13(10):110-113。
    [55]Lame PH, Steffes MW, Fioretto P, et al. Renal interstitial expansion in insulin-dependent diabetes mellitus[J].Kidney Int,1993,43(3):661-667.
    [56]Grotendorst GR. Connective tissue growth factor:a mediator of TGF-beta action on fibroblasts[J].Cytokine Growth Factor Rev,1997,8(3):171-179.
    [57]于倩张沫刘德敏TGF-β1、 CTGF基因的过表达与早期糖尿病肾病关系的研究[J].天津医药,2012,40(3):262-265。
    [58]Wang S, DenichloM, BrubakerC, et allConnective tissue growthfactor in the tubulointerstitial injury of diabetic nephropa-thylKidney Into 2001,60:96.
    [59]Riser BL, Cortes P. Connective tissue growth factor and its regulation:a new element in diabetic glomerulosclero-sis. Ren Fai,1 2001; 23 (3):459-465.
    [60]Cooper ME, Vranes D, Yonssef S, et al. Increased renal expression of vascular endothelial growth factor and its receptor VEGFR-2 in experimental Diabetes. Diabetes,1999,48:2229-2239.
    [61]王战建.王依隽:生长激素-胰岛素样生长因子轴与糖尿病肾病国外医学泌尿系统分册2005,25(3):387-390。
    [62]Elizabeth A, Cummings B, SochettGet al. Contribution of growth hormone and IGF-1 to early diabetic nephropathy in type 1 diabetes. Diabetes,1998; 47:1341~1346
    [63]PIETRASK, SJOBLOMT, RUBINK, et al. PDGF receptors as cancer drug targets [J]. Cancer Cell,2003,3(5):439-443.
    [64]关清华,王秋月,等.2型糖尿病患者PDGF-BB的变化及其对糖尿病肾病早期诊断的价值,中国医科大学学报,2008,37(1):83-85。
    [65]TANEDAS,HUDKINS KL, CUI Y, et al. Growth factor expression in amurine model of cryoglobulinemia[J].KidneyInt,2003,63(2):576-590.
    [66]Ruster C et al. Front Bioscl,2008,13:944-955。
    [67]韦丽,刘春.糖尿病肾病炎症机制的研究与防治进展[J].临床荟萃,2012:27,(1):83-85。
    [68]Giunti S,Tesch GH. Pinach S, et al. Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells [J]. Diabetologia,2008,51(1)-.198-207。
    [69]闫振成,张建国,黄志芳,等.糖尿病肾病患者单核细胞趋化蛋白-1与小管间质损害关系的研究第三军医大学学报,26(14)1291:1294。
    [70]韩婷,井源董砚虎.肿瘤坏死因子-α与糖尿病肾病[J].国际内科学杂志2009,36(7):392-398。
    [71]SzotowskiB, Antoniak S, PollerW, etallProcoagulant so-luble tissue factor is released from endothelial cells in re-sponse to inflammatory cytokineslCirc Res 2005, 96(12):1233-12391。
    [72]权晓娟,王妮,姜素珍,等.血清C-反应蛋白与2型糖尿病肾病相关分析第四军医大学学报(J).2007,28(24):2267-2268。
    [73]DeFilippi C, Wasserman S, Rosanio S, et al. CardiacTroponin T and C-reactive Protein for Predicting Prognosis, Coronary Atherosclerosis, and Cardiomyopthy inpatients Undergoing Longterm Hemodialysis [J]. JAMA,2003,290(3):353-359.
    [74]罗军,胡晓芳李言.超敏C反应蛋白和低密度脂蛋白对糖尿病肾病患者的临床意义中国试验诊断学[J].2009,13(1):140-141。
    [75]朱玲娜、唐丽琴.糖尿病肾病中氧化应激对炎症细胞因子的影响[J].安徽医药.2012,16(9):1226-1229。
    [76]武晓慧,黄颂敏.糖尿病肾病与炎症致病作用及治疗研究进展[J].华西医学,25(6)1198-1201。
    [77]陈军宁,尹友生,李小励.白细胞介素-6基因型与桂北地区2型糖尿病肾病相关性研究[J].华夏医学2009,22(5):801-804。
    [78]王光亚、葛秀兰、王绵.白细胞介素-6及其受体与糖尿病肾病[J].医学信息2003,16(3):150-151。
    [79]刘华锋,陈孝文,吴瑗,等.原发性肾小球肾炎患者肾组织白介素-18的表达[J].中华肾脏病杂志,2003,19(2):127。
    [80]:杨旭,王允洁,王桂荣TWEAK及其受体Fn14的基础研究进展[J].医学信息,2011,24(8):369-370。
    [81]Brown SA, Richards CM, Hanscom HN, Feng SL, Winkles JA. The Fn14 cytoplasmic tail binds tumour-necrosis-factor receptor-associated factors 1,2,3 and 5 and mediates nuclear factor-kappaB activation. Biochem J 2003; 371:395-403。
    [82]Carcia Bmartin-ventum JI Matinez E. et. al, Fn14 isupregulated incytokine-stulated vascule dells and is epressed in human antidachrosclerotic plaques: modiliation by atorvastatin [J]. stroke 2006.37:2044-2053。
    [83]Lynch CN, Wang YC, Lund JK. et al. TWEAK induces an-giogenesis and proliferation of endothelial cells. J Biol Chem.1999,274(13):8455—8459。
    [84]Nakayama M. Ishidoh K. Kayageki N. et al. Multiple pathways of TWEAK induc cells death. J Immunol.2002.168 (2):731-743。
    [85]Nakayama M. Kayagaki N. Yamaguchi N, et al. Involvement of TWEAK in interferon gamma-stimulated monocyte cyto-toxicity. [J].J Exp Med.2000,192(9):1373-1380.
    [86]REI KAWASHIMA, YUKI I. KAWAMURA, TOMOYUKI OSHIO, et al. Interleukin-13 Damages Intestinal Mucosa via TWEAK and Fn14 in Mice—A Pathway Associated With Ulcerative Colitis [J]. GASTROENTEROLOGY 2011;141:2119-2129。
    [87]Timothy S.Zheng, Linda C. Burkly. No end in site:TWEAK/Fn14 activation and autoimmunityassociated-end-organ pathologies. Journal of Leukocyte Biology 2008, 84:338-347=
    [88]Lynch CN, Wang YC, Lund JK. et al. TWEAK induces an-giogenesis and proliferation of endothelial cells. J Biol Chem。 1999,274(13):8455—8459.
    [89]Anak ASSK Dharmapatni, Malcolm D Smith, Tania N Crotti, et al. TWEAK and Fn14 expression in the pathogenesis of joint inflammation and bone erosion in rheumatoid arthritis (J). Arthritis Res Ther.2011; 13(2):R51。
    [90]Ana Belen Sanz, Maria D. Sanchez-Nin~o, Alberto Ortiz. TWEAK, a multifunctional cytokine in kidney injury. Kidney International (2011) 80,708-718.
    [91]Noa Schwartz, Tamar Rubinstein, Linda C Burkly et al. Urinary TWEAK as a biomarker of lupus nephritis:a multicenter cohort study, Arthritis Res Ther.2009; 11(5):R143-
    [92]复旦大学上海医学院,实用内科学编委会,陈灏珠.实用内科学(M).人民卫生出版社,2009:2307-2308。
    [93]中华中医药学会肾病分会.糖尿病肾病诊断、辨证分型及疗效评定标准[J].上海中医药杂志2007,41(7):7-8。

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700