肾白宁对糖尿病肾病大鼠模型CTGF mRNA及肾组织细胞凋亡影响的实验研究
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摘要
目的：本课题通过实验研究,观察肾白宁对糖尿病肾病模型大鼠的影响,探讨糖尿病肾病的中医发病机制及其肾白宁的作用机理,为临床合理用药奠定一定的基础。
方法：研究采用左侧肾脏摘除+STZ诱发糖尿病肾病的大鼠模型,中药组将肾白宁浸膏溶于生理盐水,配制成混悬液,以2.97g/kg(含生药量),1次／天,灌胃,2ml/次；将阳性对照组洛汀新溶于生理盐水,配制成混悬液,予以洛汀新0.9mg/kg,1次／天,灌胃,2ml/次。空白对照组及假手术组予以同体积的生理盐水溶液2ml,1次／天,灌胃。观察肾白宁对其尿微量蛋白排出量、尿NAG.ACR.实验鼠的肾重量及体重量的变化情况；采用免疫组化、RT-PCR及彩色病理图像分析系统,定性与定量检测肾组织TNF-α、Bax.Bcl-2.Co-Ⅳ、LN、FN及CTGFmRNA的表达情况；以原位末端标记法检测细胞凋亡情况。
结果：12周后光镜下可见空白对照组肾小球毛细血管球萎缩、球囊腔略增大、肾小球出入球小动脉有轻度内皮细胞增生及纤维化、基底膜略增厚,远曲小管扩张,肾间质充血、水肿、血细胞浸润、并有轻度间质纤维化。中药组与阳性对照组比较,体重量的增加程度明显优于阳性对照组,肾脏体重指数均呈下降趋势,但差异不显著。中药组在第12周时与假手术组、空白对照组相比较尿微量白蛋白、NAG、ACR有显著性差异；中药组TNF均有显著降低；肾小球中Bax、Bcl-2表达各组几乎为阴性,肾小管中Bax、Bcl-2表达假手术组显著低于其他三组,中药组与空白对照组比较细胞凋亡率显著降低、Bax阳性表达低,而Bcl-2表达高,中药组与阳性对照组比较无明显差异。空白对照组、中药组、阳性对照组肾组织CTGFmRNA较假手术组高,有显著性差异,中药组、阳性对照组与空白对照组比较阳性表达低,中药组与阳性对照组有显著性差异。
结论：肾白宁可增加实验鼠体重量,改善肾重／体重的比值,能明显改善尿微量白蛋白蛋白定量、NAG.ACR,显著降低肾组织CTGFmRNA含量,TNF-α含量,能明显抑制肾组织细胞凋亡、能明显降低Bax表达,提高Bcl-2表达,保护肾小球和肾小管结构,改善肾功能。
Objective:We observed systematically curative effect of preventing and treating Diabetic nephropathy(DN) rats by Shenbaining through clinical and experiment researches.We inquired into mechanism of traditional Chinese medicine(TCM) on DN and mechanism of Shenbaining on Preventing and treating DN.
Methods:In the study,we use the left kidney of the STZ-induced DN rat.The TCM group will dissolve shenbaining in saline, prepared into suspension and it was given 2.97g/kg,1 time/day, orally,2ml/time. The positive control group lotensin was prepared into a suspension,and also was given 0.9mg/kg,2ml/time, 1time/day, orally.Control group and the sham group to the same volume of saline solution 2m,ltime/day.Then we observed the condition of their urine protein excretion,urine NAG,ACR,rat kidney weight and body weight changes.Using immunohisto chemistry,RT-PCR and color image analysis system to qualitative and quantitative detection of kidney TNF-α,Bax,Bcl-2,ColⅣ,LN, FN and expression of CTGF mRNA.Detect cell apoptosis with the original end-labeling method.
Results:12 weeks later,it can be found in the control group that glomerular atrophy ball, balloon chamber slightly increased the glomerular afferent artery with slight endothelial cell hyperplasia and fibrosis,basement membrane thickening slightly,distal convoluted tubule expansion,renal interstitial congestion,edema,blood cell infiltration and mild interstitial fibrosis.Compared with the positive control group,the TCM group's body weight increase was significantly better,the kidney weight index were decreased,but the difference was not significant. At the 12th week,the TCM group urine albumin,NAG,ACR was significant different from the control group and the sham group;TNF condition of the TCM group were significantly lower with;Glomerular Bax, Bcl-2 expression of almost all groups were negative,tubular in Bax, Bcl-2 expression in sham group was significantly lower than the other three groups,the TCM group and the control group had significantly lower apoptosis,Bax expression is low as the expression of Bcl-2 higher,the TCM group and the positive control group showed no significant difference. The control group,the TCM group and the positive control group′s renal CTGF mRNA were higher than the sham operation group, there were significant differences.The TCM group,positive control group and blank control group expression is low,There was a significant difference between the TCM group and the positive control group.
Conclusion:Shenbaining can increase the DN rat'weight, improve the kidney weight/body weight ratio,significantly reduced renal CTGF mRNA content, TNF-αlevels,improve urinary albumin protein, NAG, ACR,inhibit renal apoptosis,decrease the expression of Bax,Bcl-2,increased the expression of glomerular and tubular structure to protect and improve renal function. NAG,ACR and microalbuminuria are more sensitive than the response to renal injury in control of renal hypertrophy.
方法：研究采用左侧肾脏摘除+STZ诱发糖尿病肾病的大鼠模型,中药组将肾白宁浸膏溶于生理盐水,配制成混悬液,以2.97g/kg(含生药量),1次／天,灌胃,2ml/次；将阳性对照组洛汀新溶于生理盐水,配制成混悬液,予以洛汀新0.9mg/kg,1次／天,灌胃,2ml/次。空白对照组及假手术组予以同体积的生理盐水溶液2ml,1次／天,灌胃。观察肾白宁对其尿微量蛋白排出量、尿NAG.ACR.实验鼠的肾重量及体重量的变化情况；采用免疫组化、RT-PCR及彩色病理图像分析系统,定性与定量检测肾组织TNF-α、Bax.Bcl-2.Co-Ⅳ、LN、FN及CTGFmRNA的表达情况；以原位末端标记法检测细胞凋亡情况。
结果：12周后光镜下可见空白对照组肾小球毛细血管球萎缩、球囊腔略增大、肾小球出入球小动脉有轻度内皮细胞增生及纤维化、基底膜略增厚,远曲小管扩张,肾间质充血、水肿、血细胞浸润、并有轻度间质纤维化。中药组与阳性对照组比较,体重量的增加程度明显优于阳性对照组,肾脏体重指数均呈下降趋势,但差异不显著。中药组在第12周时与假手术组、空白对照组相比较尿微量白蛋白、NAG、ACR有显著性差异；中药组TNF均有显著降低；肾小球中Bax、Bcl-2表达各组几乎为阴性,肾小管中Bax、Bcl-2表达假手术组显著低于其他三组,中药组与空白对照组比较细胞凋亡率显著降低、Bax阳性表达低,而Bcl-2表达高,中药组与阳性对照组比较无明显差异。空白对照组、中药组、阳性对照组肾组织CTGFmRNA较假手术组高,有显著性差异,中药组、阳性对照组与空白对照组比较阳性表达低,中药组与阳性对照组有显著性差异。
结论：肾白宁可增加实验鼠体重量,改善肾重／体重的比值,能明显改善尿微量白蛋白蛋白定量、NAG.ACR,显著降低肾组织CTGFmRNA含量,TNF-α含量,能明显抑制肾组织细胞凋亡、能明显降低Bax表达,提高Bcl-2表达,保护肾小球和肾小管结构,改善肾功能。
Objective:We observed systematically curative effect of preventing and treating Diabetic nephropathy(DN) rats by Shenbaining through clinical and experiment researches.We inquired into mechanism of traditional Chinese medicine(TCM) on DN and mechanism of Shenbaining on Preventing and treating DN.
Methods:In the study,we use the left kidney of the STZ-induced DN rat.The TCM group will dissolve shenbaining in saline, prepared into suspension and it was given 2.97g/kg,1 time/day, orally,2ml/time. The positive control group lotensin was prepared into a suspension,and also was given 0.9mg/kg,2ml/time, 1time/day, orally.Control group and the sham group to the same volume of saline solution 2m,ltime/day.Then we observed the condition of their urine protein excretion,urine NAG,ACR,rat kidney weight and body weight changes.Using immunohisto chemistry,RT-PCR and color image analysis system to qualitative and quantitative detection of kidney TNF-α,Bax,Bcl-2,ColⅣ,LN, FN and expression of CTGF mRNA.Detect cell apoptosis with the original end-labeling method.
Results:12 weeks later,it can be found in the control group that glomerular atrophy ball, balloon chamber slightly increased the glomerular afferent artery with slight endothelial cell hyperplasia and fibrosis,basement membrane thickening slightly,distal convoluted tubule expansion,renal interstitial congestion,edema,blood cell infiltration and mild interstitial fibrosis.Compared with the positive control group,the TCM group's body weight increase was significantly better,the kidney weight index were decreased,but the difference was not significant. At the 12th week,the TCM group urine albumin,NAG,ACR was significant different from the control group and the sham group;TNF condition of the TCM group were significantly lower with;Glomerular Bax, Bcl-2 expression of almost all groups were negative,tubular in Bax, Bcl-2 expression in sham group was significantly lower than the other three groups,the TCM group and the control group had significantly lower apoptosis,Bax expression is low as the expression of Bcl-2 higher,the TCM group and the positive control group showed no significant difference. The control group,the TCM group and the positive control group′s renal CTGF mRNA were higher than the sham operation group, there were significant differences.The TCM group,positive control group and blank control group expression is low,There was a significant difference between the TCM group and the positive control group.
Conclusion:Shenbaining can increase the DN rat'weight, improve the kidney weight/body weight ratio,significantly reduced renal CTGF mRNA content, TNF-αlevels,improve urinary albumin protein, NAG, ACR,inhibit renal apoptosis,decrease the expression of Bax,Bcl-2,increased the expression of glomerular and tubular structure to protect and improve renal function. NAG,ACR and microalbuminuria are more sensitive than the response to renal injury in control of renal hypertrophy.
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.
[2]林兰,倪青,董彦敏.糖尿病肾病的病因学研究述评.医学研究通讯2000(2)
[3]王自润.肾虚在消渴发病中的作用[J].中华中医药学刊2008,26(7)：1043-1045
[4]李琪,高阳,刘启庭.糖肾康治疗2型糖尿病肾病的临床研究[J],辽宁中医杂志,1998,25(3)：114-116.
[5]宋述菊,牟宗秀.糖尿病肾病病因病机及辨治探讨[J].山东中医杂志,1999,18(4)：147-148.
[6]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
[7]冯健春倪青.时振声教授治疗糖尿病肾病经验述要[J].LIAONING JOURNAL OF TRADITIONAL CHINESE MEDICINE 1996,23(12).
[8]耿嘉,栗德林.糖尿病肾病病因病机的辨析[J].首都医药,2005,n(8)：46.
[9]于文平,秦艾琳.糖尿病病因病机探讨[J].吉林中医药,1999,19(5)：4-5.
[10]黄翠玲,李才,邓义斌,等.济肾汤对搪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.
[11]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.
[12]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.
[13]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.
[14]高彦彬.中医药辨治糖尿病肾病100例临床分析[J],中医杂志,1991,32(7)：31-34.
[15]张莹雯.自拟糖肾宁治疗糖尿病肾病52例[J].黑龙江中医药,1998,27(4)：23.
[16]王洪忠,占永力.益气活血、健脾利湿法治疗糖尿病肾病26例[J].北京中医学院学报,1992,15(1)：59-60.
[17]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,1991,24(1)：1-4.
[18]李涛.糖尿病肾病的中医病机浅探[J].新疆中医药.2003,21(4)：4-5.
[19]陈翠兰.血瘀与糖尿病肾病[J].吉林中医药,2003,23(6)：8-9.
[20]李光善,邓悦.黄启福,等.毒损肾络是糖尿病肾病的病理基础[J].中医药学刊.2003,21(9)：1477-1478.
[21]邓悦.王宏,南征.糖尿病肾病从“毒损肾络”辨治理论体系探要[J].中医药学报,2003,31(3)：2-3.
[22]冼慧.糖尿病从瘀论治初探[J].中国医药学报,2000,15(2)：52
[23]杨文军,赵孔华.脾肾气机升降失常与糖尿病肾病关系探讨[J].山东中医药大学学报,2005,29(3)：188-189.
[24]王晖,王健康.糖尿病辨证论治新识[J].中医杂志,1999,40(8)：507-508.
[25]刘美奇高菁吕仁和.吕仁和教授治疗糖尿病肾病4期蛋白尿的方法[J].北京中医药大学学报(中医临床版)2003,10(4).
[26]林兰,倪青,高齐健,等.糖微康胶囊治疗糖尿病肾病的临床观察[J].中国中西医结合杂志2000,20(11).
[27]林兰,郭力.糖微康防治糖尿病肾病的临床研究[J].医学研究通讯.2003,32(5).
[28]林兰,郭力.糖微康对糖尿病肾病患者血液流变学的影响[J].中国中西医结合肾病杂志2003,4(4).
[29]罗红艳.补肾活血方治疗早期糖尿病肾病的临床研究[J].科学技术与工程2008,8(8).
[30]王焱,马显振.糖肾康胶囊治疗糖尿病肾病64例[J].河南中医2007,27(2).
[31]张丽芬,赵进喜,吕仁和,等糖尿病肾病肾功能不全防治优化方案的有效性和安全性研究[J].中外医疗2008,03
[32]朴春丽,南红梅,姜喆等.消渴肾安胶囊联合西药治疗糖尿病肾病的临床观察[J]中国中西医结合杂志2005,(25)7.
[33]朴春丽,姜喆,南征.消渴脂平胶囊治疗糖尿病肾病例疗效观察[J].新中医2005,(37)1.
[34]王福席.糖肾康治疗糖尿病肾病及其对NO、内皮素的影响[J].山东中医杂志2007,26(9).
[35]赵进喜,牟新,王世东等.止消温肾宁颗粒剂治疗糖尿病肾病肾功能不全代偿期31例临床观察[J].中医杂志2005,46(9).
[36]赵进喜王世东于秀辰等.止消通脉宁颗粒治疗糖尿病肾病肾功能不全代偿期33例疗效观察[J].河南中医2004,24(8).
[37]徐德颐徐珏.养血活血方对红细胞山梨醇、Na+-K+-ATP ase的影响[J].第九次全国中医糖尿病学术大会论文汇编,2006
[38]赵贤俊,邓悦,李光善.解毒通络保肾散治疗糖尿病肾病114例分析[J].中医药学刊 2003,21(6).
[39]南征,孙新宇,赵贤俊,南红梅,赵金祥.益肾解毒汤治疗糖尿病肾病的临床研究[J].北京中医杂志2002,21(6).
[40]宋立群,裴春鹏,宋业旭.虫草肾茶方治疗糖尿病肾病的临床研究[J].中医药信息2009,26(4).
[41]王自润.糖克煎剂防治早期糖尿病肾病实验与临床研究[J].辽宁中医药大学2009届博士学位论文
[42]冯建春.糖肾胶囊治疗糖尿病肾病的临床研究[J].中国中西医结合杂志,2000,20(3).
[43]王廷春,范冠杰,欧翠柳.加味桃核承气汤治疗糖尿病肾病138例临床观察[J].国医论坛2000,02.
[44]孙万森,吴喜利,乔成林,等.通络胶囊治疗糖尿病肾病慢性肾衰竭的临床研究[J].中国中西医结合杂志2004,08.
[45]张国山,陆连芬.益肾活血方治疗糖尿病肾病100例临床研究[J].天津中医2000，03.
[46]刘其刚.中西医结合治疗糖尿病肾病的临床研究[J].上海中医药杂志2005，02.
[47]魏连波,栗德林,叶任高,等.大黄(庶虫)虫丸对非胰岛素依赖型Ⅳ期糖尿病肾病患者Ⅷ因子相关抗原及纤维蛋白原的影响[J].中医杂志2003，01.
[48]赵华云,刘学耀.补阳还五汤对糖尿病微量白蛋白尿的影响[J].湖北中医杂志2001，07.
[49]万云莉.血府逐瘀胶囊配合西药治疗糖尿病肾病30例临床疗效观察[J].北京中医2005,01.
[50]李春桂,苗桂珍,朱学敏.益气养阴清热活血法治疗早期糖尿病肾病33例临床观察[J].河北中医2009，08.
[51]王亚敏.中西医结合治疗糖尿病肾病疗效观察[J].中国中西医结合肾病杂志,2002,3(4)：232-234.
[52]吴家瑜.辨证分型治疗糖尿病肾病58例[J].中医药学刊,2006,24(9)：1716.
[53]吕贵德.辨证论治糖尿病肾病38例疗效观察[J].河北中医,2002,24(2)：103-104.
[54]李桂芝,郑万发.中医辨证治疗糖尿病肾病100例疗效观察[J].云南中医中药杂志,2007,28(1)：17.
[55]徐延.中西医结合治疗糖尿病肾病33例[J].四川中医,2002,20(6)：38-39.
[56]林秀彬.时振声治疗糖尿病肾病经验[J].中国医药学报,2000,15(2)：74-75.
[57]曹和欣,何立群.糖肾宁对早期糖尿病肾病大鼠肾脏高滤过的影响[J].上海中医药杂志,2001,35(5)：19-21.
[58]张延群,李瑛,孔样梅,等.2080例糖尿病患者证候与并发症相关性流行病学调查报告[J].上海中医药杂志,2000,34(1)：23-25.
[59]裴宏彬,冀慧鹏.滋补肝肾法治疗糖尿病肾病临床观察[J].湖北中医杂志,2004,26(6)：11-12.
[60]钱秋海.活血化瘀防治糖尿病及并发症机制探讨[J].山东中医杂志,2002,21(3)：131-133.
[61]郑国静,常瑜,程益春.糖尿病肾病的中医治疗思路和方法[J].湖北中医杂志,2004,26(1)：23-24.
[62]李大钧,范克.糖尿病肾病的中医辨证治疗[J].河北中医,2001,23(9)：682-683.
[63]谢宗昌.糖尿病性肾病辨证施治心得[J].浙江中医杂志,2003,38(3)：128-129.
[64]王改勤,姚丽,张寒梅.辨证治疗糖尿病肾病体会[J].江西中医药,2004,38(5)：49.
[65]边芳,赵佩民,张志深,等.中西医结合治疗早期糖尿病肾病的临床观察[J].中国中西医结合杂志,2000,20(5)：335-337.
[66]潘海洋,陈琴.中西医结合治疗糖尿病肾病32例疗效观察[J].山西中医,2002,18(4)：31-32.
[67]魏军平.中药糖微康治疗糖尿病肾病的机制研究.北京中医药大学2004,硕士学位论文.
[68]杨广智.化瘀固肾散治疗糖尿病早期肾病94例临床观察[J].山西中医,2003,19(6)：14-15.
[69]周旭生.加减藿朴夏苓汤治疗糖尿病肾病32例[J].吉林中医药,2003,23(2)：16.
[70]魏玲玲.益气活血法治疗早期糖尿病肾病30例临床观察[J].中医杂志,2004,41(1)：39-40.
[71]张志忠.健脾舒肾汤治疗糖尿病肾病临床观察[J].湖北中医杂志,2004,26(6)：20.
[72]贺学林,章素云,陈以平,等.牛蒡子防治STZ糖尿病大鼠早期肾脏病变的实验研究[J].浙江中医杂志,2003,38(2)：88-90.
[73]唐红,徐蓉娟,李红,等.治糖保肾冲剂治疗早期糖尿病肾病的机理研究[J].上海中医药杂志,2002,36(4)：27-29.
[74]廖璞 王淑琴 廖雪松.银杏叶提取物对糖尿病大鼠肾脏保护作用的实验研究[J].中国药房2000,11(3).
[75]南一,南征,姜良铎.益肾通络解毒汤对糖尿病肾病大鼠肾脏功能的影响[J].吉林中医药2007,27(12).
[76]吴以岭,魏聪,贾振华,等.通肾络胶囊对糖尿病肾病大鼠肾脏蛋白激酶C通路及细胞外基质成分的影响[J].中华中医药学刊2008,02.
[77]韩永斌,徐筱玮,张德宪.糖肾平干预糖尿病肾病大鼠肾脏组织TGF—β1和FN表达的实验研究[J].光明中医2008,23(5).
[78]刘启华.肾康丸处方优化研究及其对糖尿病肾病大鼠肾皮质转化生长因子β2型受体表达的影响[J].第-军医大学论文学位硕士,
[79]陈胜.黄芪调节自发糖尿病肾病鼠层粘连蛋白表达的实验研究[J].现代生物医学进展2008,8(7).
[80]陈应强,曾家顺,李龙.黄芪对糖尿病大鼠肾组织NF-κB和MCP-1表达的影响[J]贵州医药2009,33(2).
[81]张丽芬,杨敏,赵进喜,等.黄芪卫矛合剂对糖尿病肾病大鼠尿蛋白的影响[J].中国中药杂志2008,33(2).
[82]杨敏,张丽芬,赵进喜,等.黄芪卫矛合剂对糖尿病肾病大鼠肾组织NO和ET含量影响.实用中医内科杂志.2006,20(6).
[83]苏宁,罗荣敬,苏杭,等.罗惠黄芩苷对糖尿病肾病大鼠肾功能及其抗氧化应激作用的研究[J].中药新药与临床药理.2007,18(5).
[84]郭登洲,王月华,边东等.活血化瘀消癥通络中药对糖尿病肾病大鼠肾组织血管紧张素转化酶相关羧肽酶表达的影响[J].中国全科医学2008,11(5A).
[85]宁勇,刘晓城.姜黄素对糖尿病肾病模型大鼠的防治作用[J].山东中医杂志2004,23(6).
[86]彭月芹,孔祥芬,胡宝峰,等.芪蛭消癓胶囊对糖尿病肾病大鼠肾损害的防治作 用研究[J].河南中医2008,28(5).
[87]Valmadrid CT,Klein R,Moss SE,et al.The risk of cardiovascular disease mortality associated with microalbuminuria and gross protenuria in persons with older-onset diabetes mellitus.Arch Intern Med,2000,160:1093-1100.
[88]张建国.糖尿病肾病早期诊治新进展.华南国防医学杂志,2006,20(2)：30-33.
[89]向红丁.糖尿病肾脏病变.国外医学内分泌学分册,2004,24(2)：125-136.
[90]Wu AY, Kong NC, de Leon FA, Pan CY, Tai TY, Yeung VT, et al. An alarmingly high Prev-alence of diabetic nephropathy in Asian type 2 diabetic patients:the MicroAlbuminuria Prevalenc-e (MAP) Study. Diabetologia 2005,48 (1):17-26.
[91]李红.糖尿病微血管病变发病机制和治疗靶点.浙江大学学报,2006,35(3)：232-237.
[92].Yamagishi S, TakeuchiM, Inagaki Y, et al. Role of advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic microangiopathy [J]. Int J Clin Pharmacol Res,2003,23(4):129-134.
[93]Ong ACM,Fine LG,Am J Kidney Dis,1994;23:2057-
[94]李保春,王林辉,梅小斌.糖尿病性肾病(M).上海.第二军医大学出版社,2005.
[95]SuzukiD, ToyodaM, YamamotoN, eta.l Relationship between the expression of advanced glycation end-products (AGE) and the receptor for AGE (RAGE) mRNA in diabetic nephropathy. InternMed 2006,45:435-441.
[96]Jensen LJ, Denner L, Schrijvers BF, et a.l Renal effects of a neutralizing RAGE-antibody in long-term streptozotocin-diabetic mice. JEndocrinol 2006,188: 493-501.
[97]Inoguchi T,Yu HY,Menne J,et al.Altered gap junction activity in cardiovascular tissues of diabetes.Med Electron Microse,2001,34(2):86-91.
[98]Dunlop M.Aldose reductase and the role of the polyol pathway in diabetic nephropathy.Kidney Int,2000,Suppl 77:3-12.
[99]Scocottarp V,Canz MB,Weiss MF.AGEs induce oxidative stress and activity protein kinase C-betaⅡ in neonatal mesangial cells.Am J Physiol,2000,278(4):676.
[100]Asunare K,Kahno M,Kano H,et al.Possible involvement of phospholipase and by protein kinase C in vascular growth induced by elevated glucose concentration. Hypertension,1996,28(2):159-168.
[101]Bradham DM, Igarashi A, Potter RL, et al. Connective tissue growth factor:a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10[J]. J Cell Biol,1991,114(6): 1285.
[102]Frazier K, Williams S, Kothapalli D, et al. Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor[J]. J Invest Dermatol,1996,107(3):404.
[103]Duncan MR, Frazier KS, Abramson S, et al. Connective tissue growth factor mediates transforming growth factor beta-induced collagen synthesis:down-regulation by cAMP[J]. FASEB J.1999,13(13):1774.
[104]Kothapalli D, Grotendorst GR. CTGF modulates cell cycle progression in cAMP-arrested NRK fibroblasts[J]. J Cell Physiol,2000,182(1):119.
[105]Twigg SM, Joly AH, Chen MM, et al. Connective tissue growth factor/IGF-binding protein-related protein-2 is a mediator in the induction of fibronectin by advanced glycosylation endproducts in human dermal fibroblasts[J] Endocrinology,2002,143(4):1260.
[106]Shi-wen X, Pennington D, Holmes A, et al. Autocrine overexpression of CTGF maintains fibrosis:RDA analysis of fibrosis genes in systemic sclerosis[J]. Exp Cell Res,2000,259(1):213.
[107]Grotendorst GR, Okochi H, Hayashi N. A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene[J]. Cell Growth Differ,1996,7(4):469.
[108]Chen CC, Chen N, Lau LF. The angiogenic factors Cyr61 and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts[J]. J Biol Chem,2001,276(13):10443.
[109]Fan WH, Pech M, Karnovsky MJ. Connective tissue growth factor (CTGF) stimulates vascular smooth muscle cell growth and migration in vitro[J]. Eur J Cell Biol,2000,79(12):915.
[110]Shimo T, Nakanishi T, Kimura Y, et al. Inhibition of endogenous expression of connective tissue growth factor by its antisense oligonucleotide and antisense RNA suppresses proliferation and migration of vascular endothelial cells[J]. J Biochem Tokyo,1998,124(1):130.
[111]Babic AM, Chen CC, Lau LF. Fisp12/mouse connective tissue growth factor mediates endothelial cell adhesion and migration through integrin alphavbeta3, promotes endothelial cell survival, and induces angiogenesis in vivo[J]. Mol Cell Biol, 1999,19(4):2958.
[112]Kondo S, Kubota S, Shimo T,et al. Connective tissue growth factor increased by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases[J]. Carcinogenesis,2002,23(5):769.
[113]Nakanishi T, Kimura Y, Tamura T, et al. Cloning of a mRNA preferentially expressed in chondrocytes by differential display PCR from a human chondrocytic cell line that is identical with connective tissue growth factor (CTGF) mRNA[J]. Biochem Biophys Res Commun,1997,234(1):206.
[114]Xu J, Smock SL, Safadi FF, et al. Cloning the full-length cDNA for rat connective tissue growth factor:implications for skeletal development[J]. J Cell Biochem,2000, 77(1):103.
[115]Folger PA, Zekaria D, GrotendotGet al. Transforming growth factor-beta stimulated connective tissue growth factor expression during cornealmyofibroblast differentiation. Invest-OphthalMol Uis Sc,i 2001,42 (11):2534-2541
[116]Wahab NA, Brinkman H, Mason RMet al. Uptake and intracellular transport of the connective tissue growth factor:a potentialmode of action. Biochem J,2001,359 (ptl)89-97
[117]Min Yang, Haichang Huang, Jingzi Liet al. Tyrosine phosphorylation of the LDL receptor-related protein (LRP) and activation of the ERK pathway are required for connective tissue growth factor to potentiate myofibroblast differentiation. FASEBJ, 2004,18 (15):1920-1921
[118]Wahab NA, Mason RM. Connective tissue growth factor and renal diseases:some answers, more questions. CurrOpin NephrolHypertens,2004,13:53-58
[119]ItoY, Bende RJ, OemarBSet al. Expression of connective tissue growth factor in human renal fibrosis. Kidney Int,1998,53 (4):853-861
[120]MurphyM, Godson C, Cannon Set al. Suppression subtractive hybridization identifies high glecose levels as a stimuls for expression of connective tissue growth factor and other genes in human mesangial cells. J Biol Chem,1999,74 (9):5830-5834
[121]Riser BL, Denichilo M, Cortes Pet al. Regulation of connective tissue growth factor activity in cultured ratmesangial cells and its expression experimental diabetic glomerulosclerosis. JAm SocNephro,l 2000,1 (1):25-38
[122]Riser BL, Denichilo M, Cortes Pet al·Regulation of connective tissue growth factor activity in cultured rat mesangial cells and its expression in experimental diabetic glomerulosclerosis·JAmSoc Neprol,2000,11:25
[123]Mason RM, Li X, Wahab NA·High glucose induces the expression of connective tissue growth factor in human mesangial cells·J Am Soc Nephrol,1997,8:624A
[124]Murphy M, Godson C, Cannon Set al·Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells·J Biol Chem,1999,274:5830
[125]Wang S, Denichlo M, Brubaker Cet al·Connective tissue growth factor in the tubulointerstitial injury of diabetic nephropathy·Kidney Int,2001,60:96
[126]Wahab NA, Yevdokimova N, Weston BSet al·Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy·Biochem J,2001,359:77
[127]Adler SG, Kang SW, Feld Set al·Glomerular mRNAs in human type 1 diabetes: biochemical evidence for miroalbuminuria as a manifestation of diabetic nephropathy·Kidney Int,2001,60:2330
[128]Wahab NA, Weston BS, Robet Tet al·Connective tissue growth factor and regulation of the mesangial cell cycle:role in cellular hypertrophy·J Am Soc Nephrol, 2002,13:2437
[129]Ito Y, Goldschmeding R, Bende RJet al·Kinetics of connective tissue growth factor expression during experimental proliferative glomerulonephritis·J Am Soc Neprol,2001,12:472
[130]黄海长,李惊子,王海燕·结缔组织生长因子诱导肾成纤维细胞转化成肌成纤维细胞。科学通报,2002,47(1)：37
[131]Twigg SM, Chen MM, Joly AHet al·Advanced glycosylation end products up-regulate connective tissue growth factor (insulin-like growth factor-binding protein-related protein-2) in human fibroblasts:a potential mechanism for expansion of extracelluar matrix in diabetic mellitus·Endocrinology,2001,142(5):1760
[132]Twigg SM, Joly AH, Chen MMet al·Connective tissue growth factor/IGF-binding protein-related protein-2 is a mediator in the induction of fibronectin by advanced glycosylation end products in human dermal fibroblasts·Endocrinology,2002,143(4):1 260
[133]Alder SG, KangSW, Feld Set al·Can glomerularmRNAs in type 1 diabetes be used to predict transition from normoalbumunuria to microalbuminuria? Am J Kidney Dis, 2002,40(1):184
[134]Ayer-leliever A, Brigstock D, Lau Let al·Report on the first international workshop on the CCN family of genes·J Clin Pathol,2001,54:105
[135]Igarashi A, Okochi H, Bradham Dm, et al. Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair[J]. Mol Biol Cell,1993,4(6):637.
[136]Mori T, Kawara S, Shinozaki M, et al. Role and interaction of connective tissue growth factor with transforming growth factorbeta in persistent fibrosis:A mouse fibrosis model[J]. J Cell Physiol,1999,181(1):153.
[137]周勇,朱健,王奕.细胞因子与2型糖尿病及胰岛素抵抗的相关性研究[J].中国医师进修杂志,2006,29(1)：42-44.
[138]王艳军,韩萍,卢丽萍.糖尿病肾病患者体内IL-6, TNF-α及TGF-β检测及临床意义的分析[J].中国免疫学杂志,2002,18(3)：214-216.
[139]Lofgren P,Van Harmelen V,Reynisdottir S,et al.Secretion of tumor necrosis factor-alpha shows a strong relationship to insulin-stimulated glucose transport in human adipose tissue[J].Diabetes,2000,49(4):688-692.
[140]Amore A,Crina P,Mitola S,et al.Nonenzvmatically glycated albumin(Amadori adducts)enhances nitric oxide synthase activity and gene expression in endothelial cells[J].Kidney Int,1997,51 (1):27-35.
[141]栗德林,苑讯.糖肾康对实验性大鼠ET-1、TNF、 IL-6等的影响[J].中医药信 息,2003,20(2)：57-58.
[142]肖常青,梁瑜祯,苏宏业,等.糖尿病人血浆肿瘤坏死因子α变化及其相关因素研究[J].中国糖尿病杂志,2001,6(9)：369-370.
[143]刘震宇,成兴波,蒋晓红,等.血清TNF-a与2型糖尿病肾病的相关性研究[J]南通大学学报200,06.
[144]Abraham DJ, Shiwen X, Black CM, et al. Tumor necrosis factor alpha suppresses the induction of connective tissue growth factor by transforming growth factor-beta in normal and scleroderma fibroblasts[J]. J Biol Chem,2000,275(20):15220.
[145]Dammeier J, Beer HD, Brauchle M, et al. Dexamethasone is a novel potent inducer of connective tissue growth factor expression.Implications for glucocorticoid therapy[J]. J Biol Chem,1998,273(29):18185.
[146]Chambers RC, Leoni P, Blanc-Brude OP, et al. Thrombin is a potent inducer of connective tissue growth factor production via proteolytic activation of protease-activated receptor-l[J].J Biol Chem,2000,275(45):35584.
[147]Schild C,Trueb B.Mechanical stress is required for high-level expression of connective tissue growth factor[J].Exp Cell Res,2002,274(1):83.
[148]Kessler D,Dethlefsen S,Haase I,et al.Fibroblasts in mechanically stressed collagen lattices assume a"synthetic"phenotype[J]JBiol Chem,2001,276(39):36575.
[149]贾汝汉,陈玲.氧化应激在糖尿病肾病发病中的作用(上).中国中西医结合肾病杂志,2006,7(8)：373-375
[150]Maritim AC,SandersRA,Watkins JB. Diabetes, ox-idative stress, and antioxidants: a review. JBiochemMolToxico,1 2003,17:24-38.
[151]BrownleeM.Biochemistry andmolecular cell biology of diabetic comp lications. Nature,2001,414:813-820.
[152]XuY,OsborneBW,StantonRC.DiabetesCauses Inhibition ofGlucose 6-Phosphate Dehydrogenase via Activation of Protein Kinase A which Contributes toOxidative Stress inRatKidneyCortex.Am JPhysiolRenalPhysio,l 2005,289(5):1040-1047.
[153]陈玲,贾汝汉,丁国华,等.缬草油对2型糖尿病大鼠肾脏的保护作用及其机制探讨.中华肾脏病杂志,2003,19(3)：168-172.
[154]AksunAS,Ozmen B,OzmenD,et al.Serum and urinary nitric oxide in Type 2 diabeteswith orwithoutmicroalbuminuria:relation toglomerular hyperfiltration. JDiabetes Complications,2003,17(6):343-348.
[155]Banda N,Nakamura T,MatsumuraM,et al.Possible relationship of monocyte chemoattratant protein-1 with diabetic nephropathy. Kinney In,t 2000,58(2):684-686.
[156]ScivittaroV,GanzMB,WeissMF.AGEs induce oxidative stressand activate protein kinaseC-beta(Ⅱ)in neotalmesangialcells.Am JPhysiol RenalPhysio,l 2000,278 (4): 676-678.
[157]SusztakK,RaffAC, SchifferM, et al.Glucose-induced reactive oxygen species cause apoptosisofpodocytesand podocyte depletion atthe onset ofdiabetic nephropathy. Diabetes,2006,55(1):225-233.
[158]HaH,YuMR, ChoiYJ, et a.l Role of high glucose-induced nuclear factor-kappaB activation in monocyte chemoattractant protein-1 expression by mesangial cells. J Am Soc Nephro,l 2002,13 (4):894-902.
[159]MoriiT, FujitaH,Narita T, et al. Association ofmonocyte chemoat tractantprotein-1 with renal tubulardamage in diabetic nephropathy.J Diabetes Complications, 2003,17(1):11-15.
[160]成宏,陈允硕,巫向前.层粘连蛋白的生物学特性研究现状及应用[J].国外医学·临床生物化学与检验学分册,1995,16(5)：217
[161]Kreisberg JI,Ayo SH.The Glomerular Mesangiumin Diabetes Mellitus [J].Kidney Int,1993,43:109-110
[162]汪洪流.Ⅱ型糖尿病肾病和红细胞膜ATP酶活性的关系.《淮海医药》2001年6月第19卷第3期
[163]Simchons,Gavin JR.Influence of reduced red cell deformability onregional blood flow[J].Am J Phyiol,1987:253,898
[164]丁国宪,陈家伟,何戎华,等.Ⅱ型糖尿病伴高血压机制探讨[J].中华内分泌代谢杂志,1995,4(11)：214
[165]王尧,成必成,腾航,等.糖尿病肾病患者红细胞膜上Na+、K+-ATP酶及Ca2＋、 Mg2+-ATP酶活性的变化[J].南京铁道医学院学报,1998,17(2)：123
[166]卢欣萍,欧阳安,苏天水,等.糖尿病患者红细胞膜钙、镁ATP酶研究[J].中华内分泌代谢杂志,1992,8(3)：155
[167]Maxfield EK,Cameron NE,Cotter MA.Effects of diabetes on reactivity of sciatic vasa nervorum in rat.J Diabetes Compl,1997,11(1):47-55.
[168]刘东方,严中德,沈鼎明,等.糖尿病自主神经病变和糖尿病肾病关系探讨.中国糖尿病杂志,1998,2(1)：6.
[169]Michimata T,Murakami M,Iriuchijima T.Nitric oxide-dependent soluble guanylate cyclase activity is decreased in platelets from male NIDDM patient.Life Sci,1996,59:1463-1471.
[170]Agewall S.Insulin sensitivity and haemostatic factors in men at high and low cardiovascular risk.J Intern Med,1999,246:489-495.
[171]Karamanos B,Porta M,Songini M,et al.Different risk factors of microangiopathy in patients with type 1 diabetes mellitus of short versus long duration:the Eurodiab IDDM Complications Study.Diabetologia,2000,43:348-355.
[172]NeuhoferW, Pittrow D-Role of endothelin and endothelin receptor antagonists in renal disease·Eur J Clin Invest,2006,36 (Surppl3):78-88
[173]Hargrove GM, Dufresne J, Whiteside Cet al. Diabetesmellitus increases endothelin-1 gene transcription in ratkidney. Kidney Int,2000,58 (4):1534-1545
[174]Lopez-Ongil S, Diez-MarquesML, GrieraMet al. Crosstalk betweenmesangialand endothelial cells:angiotensin Ⅱ down-regulates endothelin-converting enzyme 1-Cell PhysiolBiochem,2005,15 (1-4):135-144
[175]KuoHT, Shin SJ, KuoMCet al. Effects of specific endothelin-1 receptor antagonists on proliferation and fibronectin production of glomerularmesangial cells stimulated with Angiotensin Ⅱ·Kaohsiung JMed Sc,i 2006,22 (8):371-376
[176]ItohY, NakaiA, KakizawaHet al. Alteration of endothel in-1 concentration in STZ-induced diabetic ratnephropathy·Effects of a PGI (2) derivative-Horm Res, 2001,56(5-6):165-171
[177]ChenHC, Guh JY, Shin SJet al. Reactive oxygen species enhances endothelin-1 production of diabetic rat glomeruli in vitro and in vivo·JLab ClinMed,2000,135 (4): 300-302
[178]Ak G, Buyukberber S, Sevinc Aet al. The relation between plasma endothelin-1 levels and metabolic contro,l risk fators, treatmentmodalities, and diabetic microangiopathy in patients with Type 2 diabetes mellitus-J Diabetes Complications, 2001,15 (3):150-157
[179]Bruno CM,Meli S,MarcinnoMet al.Plasma endothelin-1 levels and albumin excretion rate in normotensive, microalbuminuric type 2 diabetic patients-J Biol Regul HomeostAgents,2002,16 (2):114-117
[180]叶山东.内皮素和糖尿病肾脏病变.国外医学·泌尿系统分册,1997,17(1)：35-37
[181]陈明,黄颂敏.内皮素、-氧化氮与糖尿病肾病[J].国外医学内分泌学分册,1999,2(19)：89-72.
[182]Zhang W,Khanna P,Chan LL,et al.Diabetes induced apoptosis in rat kidney[J].Biochem Mol Med,1997,61(1):58-62.
[183]Sugiyama H,Kashihara N,Makino H,et al.Apoptosis in glomerular sclerosis [J].Kidney Int,1996,49(1):103-111.
[184]Ortriz A,Ziyadeh FN,Neilson EG.Expression of apoptosis-regulatory gene in renal proximal tubular epithelial cells exposed to high ambient glucose and in diabetic kidneys.JInvest Med,1997,45(2):50-56.
[185]Uda S,Yoshimura A,Sugenoya Y,et al.Mesangial proliferative nephritis in man is associated with increased expression of the cell srrvival factor,bcl-2.Am J Neprol,1998,18:291-295.
[186]康健,羊惠君,李爱冬.糖尿病早期大鼠肾小管上皮细胞凋亡与增殖的观察.川北医学院学报,1999,14(2)：4-6.
[187]Harrison DJ.Cell death in the diseased glomerulus.Histopathology,1988, 12:679-683.
[188]Shimizu A,Kitamura H,Masuda Y,et al.Apoptosis in the repair process of experimental proliferative glomerulonephritis.Kidney Int,1995,47:114-121.
[189]Sugiyama H,Kashihara N,Makino H,et al.Apoptosis in glomerular sclera-sis.Kidney Int,1996,49:103-111.
[190]Shimizu A,Masuda Y,Kitamura H,et al.Apoptosis in progressive crescentic glomerulonephritis. Lab Invest,1996,74:941-951.
[191]Gauer S,Yao J,Schoedklmann HO,et al.Adhesion molecules in the glomerular mesangi um.Kidney Int,1997,51:1447-1153.
[192]Kitamura M and Ishikawa Y.Three-dimensional matrix primes mesangial cells to downregulation of alpha smooth muscle actin via deactivatiom of GArG box elements.Kidney Int,1998,53:690-697.
[193]Sugiyama H,Kashihara N,Maeshima Y,et al.Regulation of survival and death of mesangial cells by extracellular matrix.Kidney Int,1998,54:1188-1196.
[194]Johnson RJ,Floege J,Yoshimura A,et al.The activated mesangial cell:a glomertular myofibroblast? J Am Soc Nephrol,1992,2:190-197.
[195]White E.Life,death,and the pursuit of apoptosis[J].Genes Dev,1996,10(1):1-15.
[196]Korsmeyer SJ.Bcl-2 gene family and the regulation of programmed cell death [J].Cancer Res,1999,59(7 Suppl):1693s-1700s.
[197]张艳玲,段惠军,李春香,等.糖尿病大鼠肾脏细胞凋亡与Bax和Bcl-2基因表达[J].中国糖尿病杂志,2002,10(3)：159-162.
[198]Yang B,Jonnson TS,Thoamas GL,et al.Expression of apoptosisrelated genes and proteins in experimental chronic renal scarring [J].J Am Soc Nephrol,2001,12(2): 275-288.
[199]Gobé GC,Zhang XJ.Relationship between expression of Bcl-2 genes and growth factors in ischemic acute renal failure in the rat [J] J Am Soc Nephrol,2000, 11(3):454-467.
[200]苏君梅,董峰,易华,等.糖尿病大鼠肾脏细胞凋亡的研究[J].武汉大学学报(医学版),2003,24(1)：17-20.
[201]张新爽,刘亚玲,张艳玲.苯那普利对糖尿病大鼠肾脏细胞凋亡及Fas和Fas-L表达的影响[J].河北医药,2003,25(4)：243-245.
[202]段惠军,张艳玲,史永红,等.苯那普利对糖尿病大鼠肾脏细胞凋亡的影响[J].药学学报,2002,37(6)：409-411.
[203]赵玲,顾江萍,贾德林,等.细胞凋亡与糖尿病肾病的关系及糖肾康作用机制的研究[J].中国中西医结合肾病杂志,2003,4
[204]Mogensen CE.Mieralbuminuria as apredietor of clinieal diabetie nePhOPathy kidney Int,1987:67-75
[205]王吉耀.内科学(下册),北京：人民卫生出版社,2005,第-版：981
[206]张蕙芬,迟家敏,王瑞萍.实用糖尿病学,北京：北京：人民卫生出版社,2004,第二版：364-365
[207]张秀珍,李素.内分泌代谢疾病与肾脏,上海：复旦大学出版社,2004,第-版：115-116
[208]王晓光,姚源漳.肾脏病诊断与治疗,北京：人民军医出版社,2006,第-版：105-106
[209]KozlowskaL, Rosolowska-HuszczD, RydzewskiA·[J]·Nephrology (Carlton),2004, 9 (5):319-324(?)
[210]HansenHP, Tauber-Lassen E, Jensen BR, et al·[J]·Kidney Int,2002,62(1): 220-228(?)
[211]MitchWE·[J]·Kidney Int,2005,4(94):S133-135(?)
[212]Feiten SF,Draibe SA,Watanabe R, et al·[J]·Eur J Clin Nutr,2005,59(1):129-136(?)
[213]American Diabetes Association·[J]·Diabetes Care,2004,27(Suppll):S79-83(?)
[214]Diabetes Control and Complications Trial-Epidemi-ology of Diabetes Interventions and Complications Research Group.[J].JAMA,2003,290 (16):2159-2167(?)
[215]Sarafidis PA,Lasaridis AN,Nilsson PM,et al.[J].Am J Hypertens,2005,18 (2 Pt 1): 227-234(?)
[216]ParvingHH, LehnertH, Brochner-Mortensen J, et al.[J].N Engl JMed,2001, 345(12):870-878(?)
[217]Lewis EJ,HunsickerLG,ClarkeWR,et al.[J].N Engl JMed,2001,345(12):851-860(?)
[218]RemiuzziG, RuggenentiP, PernaA,et al.[J].J Am Soc Nephro,l 2004,15(12): 3117-3125(?)
[219]BarnettAH, Bain SC, BouterP, etal·[J]·N Engl JMed,2004,351(19):1952-1961(?)
[220]Mogensen CE,Neldam S,Tikkanen I,et al·[J]·BMJ,2000,321(7274):1440-1444(?)
[221]American Diabetes Association·[J]·DiabetesCare,2005,28(Suppll):S4-S36(?)
[222]Moriyama T,Oka K,Ueda H,et al·[J]·Clin Exp Nephro,l 2004,8(3):230-236(?)
[223]RuggenentiP,FassiA,Ilieva AP, et al·[J]·N Engl JMed,2004,351(19):1941-1951(?)
[224]RachmaniR,Slavachevsky I,AmitM, etal·[J]·DiabeticMed,2004,21(5):471-475(?)
[225]Shah S,Paparello J,Danesh FR·[J]·AdvChronic KidneyDis,2005,12(2):187-195(?)
[226]Thallas-Bonke V,Lindschau C,Rizkalla,et al·[J]·Diabetes,2004,53(11): 2921-2930.
[227]Alderson NL,Chachich ME,Frizzell N,et al·[J].Diabetologia,2004,47(8): 1385-1395.
[228]LalMA,BrismarH,EklofAC,et al·[J]-Kidney Int,2002,61(6):2006-2014-
[229]ArticoM,De Santis S,TranquilliLealiFM, et al·[J]·JDiabetes Complications,2004, 18(2):119-125.
[230]Tohma T,ShimabukuroM,OshiroY,et al-[J]·Metabolism,2004,53(11):1405-1410
[231]Mankhey RW,Bhatti F,Maric C·[J]·Am J PhysiolRenalPhysiol.2005,288(2): F399-405.
[232]叶跃红,高科,李兴禄.尿沉渣分析和尿微量白蛋白在早期糖尿病肾病中的临床应用[J].重庆医学,2003,32(12)：1642.
[233]邓晓初.尿白蛋白／肌酐比值检测法在早期2型糖尿病肾病中的应用[J].重庆医学,2005,34(1)：46.
[234]Kanauchi M,Dohi K.Predictorsof diabetic renal lesions in type 2 diabetes associated with microalbuminuria.Eur J Clin Invest,2001,31 (2):110.
[235]Lenley KV,Abolillah I,MyersBD,et al.Evolution of incipient nephropathy in type 2 diabetesmellitus.Kidney Int,2000,58 (3):1228.
[236]王艳萍等.NAG及β2-微球蛋白联合检测对糖尿病肾病早期诊断的意义[J]中国医科大学学报2004,(33)1.
[237]刘振平,张艳玲,陆菊明·糖尿病肾病的标记物[J].中华肾脏病杂志,1999,15(6)：389-391.
[238]陈澍,刘雪芳.链脲佐菌素诱导大鼠糖尿病肾病模型的建立[J].实用医学杂志,2006,22(11)：1239-1240.
[239]宋恩峰等.2型糖尿病肾病大鼠模型制备研究实用医学杂志2007,23(18)
[240]高苹.2型糖尿病肾病大鼠模型的建立.中国中西医结合肾病杂志2007,8(6).
[241]杨钱红.贝那普利对糖尿病肾病患者尿微量白蛋白的影响。吉林医学,Jilin Medical Journal,编辑部邮箱2010年04期
[242]Lewei EJ,Hunsieker LG,Bain Rp,etal.The efeet of angiotensin converting enzyme inhibition on diabetie nePhorPathy.The Collaborative Study GoruP.N Eng J Med,1993, 329:1456-1462.
[243]Rveid M,Savin HJutrin I,etal.Long-term stabilizing efeet of angiotensin Converting enzyme inhibition on Plasma ereatinine and on Porteinuriain Nomrotensive tyPe Ⅱ diabetie Patients,Ann IntenrMed,1993,118:577-581.
[244]Heart outeomes Prevention Evaluation (HOPE)Study Investigators. Effeets of ramiPril on aeluiovaseular and mieorvaseular outeomes in PeoPle with diabetes mellitus:results of the HOPE Study and MICRO-HOPE Substudy Laneet,2000,355: 253-259
[245]王苏杭.血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂治疗糖尿病肾病的新进展,安徽医药,2005,9(5)：356-355.
[246]邹敏书刘雪梅余健轰国明。贝那普利和维生素E对糖尿病肾病大鼠氧化应激的影响。中目药师2的7年第10卷第6期Pharmaeis,,vol.1ONo.6
[247]赵进喜,邓德强,李靖.糖尿病肾病相关中医病名考辨,南京中医药大学学报(自然科学版),2005,21(5)：288-289.
[248]清·张秉成.《成方便读·卷之-》.上海科技出版社,1963：9.
[249]明·张锡纯.《医学衷中参西录》.中国文史出版社,北京,2003：34.6
[250]清·吴仪洛.《本草从新》.大津科技出版社,天津.2003：43.
[251]清·黄宫绣.《本草求真》.上海科技出版社,上海,195.9
[252]明·张锡纯.《医学衷中参西录》.中国文史出版社,北京,2003：350.
[253]中药大词典.上海科学技术出版社,1993第三版上册,166-16.8
[254]中药大词典.上海科学技术出版社,1993第二版上册,1127-113.0
[255]中药人词典.上海科学技术出版社,1993第止版下册,1596-159.9
[256]中药大词典.上海科学技术出版社,1993第二版上册,517-51.9
[257]雷载权等.《中药学》第六版.上海科技出版社.1999,90-325.
[258]陈力真等.地黄多糖b对荷肉瘤180例小鼠T淋巴细胞的作用.中国药理学报,1995,16(4)：337.
[259]石君华.黄芪对实验性MD人鼠肾脏保护作用的实验研究.[J]中国中医药科技,2000,6(5)：314.
[260]马子密,傅延龄土编.历代本草药性汇解.中国医药科技出版社,2002第-版,214-219.
[261]范幼箔.当归改善老年糖尿病肾病功能的研究.[J]中国老年杂志,1996,16：77.
[262]董柯等.水蛭对系膜增殖性肾炎蛋白尿、脂质代谢及凝血机制的影响.中华内科杂志,1995,34(4)：250.
[263]马子密,傅延龄土编.历代本草药性汇解.中国医药科技出版社,2002第-版,5-5.
[264]Gilbert RE, Akdeniz A,Weitz S, et a.l Urinary connective tissue growth factor excretion in patientswith type 1 diabetes and nephropathy.DiabetesCare,2003,26: 2632-2636.
[265]Mason RM,Wahab NA. Extracellular matrix metabolism in diabetic nephropathy. JAm SocNephro,1 2003,14:1358-1373.
[266]Hashimoto G, Inoki I, FujiiY, et a.l Matrixmetalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor165. J BiolChem,2002,277:36288-36295.
[267]Twigg SM,CooperME.The time has come to target connective tissue growth factor in diabetic com-plications.Diabetologia,2004,47:965-968.
[268]Mclennan SV,WangXY,MorenoV, et a.l Connective Tissue Growth Factor MediatesHigh Glucose Effects on Matrix Degradation through Tissue Inhibitor ofMatrixMetalloproteinase Type 1:Implications for Diabetic Nephropathy. Endocrin-ology,2004,145:5646-5655.
[269]Twigg SM,CaoZ, SVMC, eta.l Renal connective tissue growth factor induction in experimental diabetes is prevented by aminoguanidine.Endocrinology,2002,143: 4907-4915.
[270]Andersen S, van Nieuwenhoven FA,Tarnow L, et a.l Reduction of urinary conn-ective tissue growth factor by Losartan in type 1 patients with diabetic nephro-pathy.Kidney Int,2005,67:2325-2329.
[271]涂晓文.结缔组织生长因子：糖尿病肾病治疗的新靶点.国际泌尿系统杂志2006,26(1).
[2]林兰,倪青,董彦敏.糖尿病肾病的病因学研究述评.医学研究通讯2000(2)
[3]王自润.肾虚在消渴发病中的作用[J].中华中医药学刊2008,26(7)：1043-1045
[4]李琪,高阳,刘启庭.糖肾康治疗2型糖尿病肾病的临床研究[J],辽宁中医杂志,1998,25(3)：114-116.
[5]宋述菊,牟宗秀.糖尿病肾病病因病机及辨治探讨[J].山东中医杂志,1999,18(4)：147-148.
[6]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
[7]冯健春倪青.时振声教授治疗糖尿病肾病经验述要[J].LIAONING JOURNAL OF TRADITIONAL CHINESE MEDICINE 1996,23(12).
[8]耿嘉,栗德林.糖尿病肾病病因病机的辨析[J].首都医药,2005,n(8)：46.
[9]于文平,秦艾琳.糖尿病病因病机探讨[J].吉林中医药,1999,19(5)：4-5.
[10]黄翠玲,李才,邓义斌,等.济肾汤对搪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.
[11]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.
[12]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.
[13]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.
[14]高彦彬.中医药辨治糖尿病肾病100例临床分析[J],中医杂志,1991,32(7)：31-34.
[15]张莹雯.自拟糖肾宁治疗糖尿病肾病52例[J].黑龙江中医药,1998,27(4)：23.
[16]王洪忠,占永力.益气活血、健脾利湿法治疗糖尿病肾病26例[J].北京中医学院学报,1992,15(1)：59-60.
[17]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,1991,24(1)：1-4.
[18]李涛.糖尿病肾病的中医病机浅探[J].新疆中医药.2003,21(4)：4-5.
[19]陈翠兰.血瘀与糖尿病肾病[J].吉林中医药,2003,23(6)：8-9.
[20]李光善,邓悦.黄启福,等.毒损肾络是糖尿病肾病的病理基础[J].中医药学刊.2003,21(9)：1477-1478.
[21]邓悦.王宏,南征.糖尿病肾病从“毒损肾络”辨治理论体系探要[J].中医药学报,2003,31(3)：2-3.
[22]冼慧.糖尿病从瘀论治初探[J].中国医药学报,2000,15(2)：52
[23]杨文军,赵孔华.脾肾气机升降失常与糖尿病肾病关系探讨[J].山东中医药大学学报,2005,29(3)：188-189.
[24]王晖,王健康.糖尿病辨证论治新识[J].中医杂志,1999,40(8)：507-508.
[25]刘美奇高菁吕仁和.吕仁和教授治疗糖尿病肾病4期蛋白尿的方法[J].北京中医药大学学报(中医临床版)2003,10(4).
[26]林兰,倪青,高齐健,等.糖微康胶囊治疗糖尿病肾病的临床观察[J].中国中西医结合杂志2000,20(11).
[27]林兰,郭力.糖微康防治糖尿病肾病的临床研究[J].医学研究通讯.2003,32(5).
[28]林兰,郭力.糖微康对糖尿病肾病患者血液流变学的影响[J].中国中西医结合肾病杂志2003,4(4).
[29]罗红艳.补肾活血方治疗早期糖尿病肾病的临床研究[J].科学技术与工程2008,8(8).
[30]王焱,马显振.糖肾康胶囊治疗糖尿病肾病64例[J].河南中医2007,27(2).
[31]张丽芬,赵进喜,吕仁和,等糖尿病肾病肾功能不全防治优化方案的有效性和安全性研究[J].中外医疗2008,03
[32]朴春丽,南红梅,姜喆等.消渴肾安胶囊联合西药治疗糖尿病肾病的临床观察[J]中国中西医结合杂志2005,(25)7.
[33]朴春丽,姜喆,南征.消渴脂平胶囊治疗糖尿病肾病例疗效观察[J].新中医2005,(37)1.
[34]王福席.糖肾康治疗糖尿病肾病及其对NO、内皮素的影响[J].山东中医杂志2007,26(9).
[35]赵进喜,牟新,王世东等.止消温肾宁颗粒剂治疗糖尿病肾病肾功能不全代偿期31例临床观察[J].中医杂志2005,46(9).
[36]赵进喜王世东于秀辰等.止消通脉宁颗粒治疗糖尿病肾病肾功能不全代偿期33例疗效观察[J].河南中医2004,24(8).
[37]徐德颐徐珏.养血活血方对红细胞山梨醇、Na+-K+-ATP ase的影响[J].第九次全国中医糖尿病学术大会论文汇编,2006
[38]赵贤俊,邓悦,李光善.解毒通络保肾散治疗糖尿病肾病114例分析[J].中医药学刊 2003,21(6).
[39]南征,孙新宇,赵贤俊,南红梅,赵金祥.益肾解毒汤治疗糖尿病肾病的临床研究[J].北京中医杂志2002,21(6).
[40]宋立群,裴春鹏,宋业旭.虫草肾茶方治疗糖尿病肾病的临床研究[J].中医药信息2009,26(4).
[41]王自润.糖克煎剂防治早期糖尿病肾病实验与临床研究[J].辽宁中医药大学2009届博士学位论文
[42]冯建春.糖肾胶囊治疗糖尿病肾病的临床研究[J].中国中西医结合杂志,2000,20(3).
[43]王廷春,范冠杰,欧翠柳.加味桃核承气汤治疗糖尿病肾病138例临床观察[J].国医论坛2000,02.
[44]孙万森,吴喜利,乔成林,等.通络胶囊治疗糖尿病肾病慢性肾衰竭的临床研究[J].中国中西医结合杂志2004,08.
[45]张国山,陆连芬.益肾活血方治疗糖尿病肾病100例临床研究[J].天津中医2000，03.
[46]刘其刚.中西医结合治疗糖尿病肾病的临床研究[J].上海中医药杂志2005，02.
[47]魏连波,栗德林,叶任高,等.大黄(庶虫)虫丸对非胰岛素依赖型Ⅳ期糖尿病肾病患者Ⅷ因子相关抗原及纤维蛋白原的影响[J].中医杂志2003，01.
[48]赵华云,刘学耀.补阳还五汤对糖尿病微量白蛋白尿的影响[J].湖北中医杂志2001，07.
[49]万云莉.血府逐瘀胶囊配合西药治疗糖尿病肾病30例临床疗效观察[J].北京中医2005,01.
[50]李春桂,苗桂珍,朱学敏.益气养阴清热活血法治疗早期糖尿病肾病33例临床观察[J].河北中医2009，08.
[51]王亚敏.中西医结合治疗糖尿病肾病疗效观察[J].中国中西医结合肾病杂志,2002,3(4)：232-234.
[52]吴家瑜.辨证分型治疗糖尿病肾病58例[J].中医药学刊,2006,24(9)：1716.
[53]吕贵德.辨证论治糖尿病肾病38例疗效观察[J].河北中医,2002,24(2)：103-104.
[54]李桂芝,郑万发.中医辨证治疗糖尿病肾病100例疗效观察[J].云南中医中药杂志,2007,28(1)：17.
[55]徐延.中西医结合治疗糖尿病肾病33例[J].四川中医,2002,20(6)：38-39.
[56]林秀彬.时振声治疗糖尿病肾病经验[J].中国医药学报,2000,15(2)：74-75.
[57]曹和欣,何立群.糖肾宁对早期糖尿病肾病大鼠肾脏高滤过的影响[J].上海中医药杂志,2001,35(5)：19-21.
[58]张延群,李瑛,孔样梅,等.2080例糖尿病患者证候与并发症相关性流行病学调查报告[J].上海中医药杂志,2000,34(1)：23-25.
[59]裴宏彬,冀慧鹏.滋补肝肾法治疗糖尿病肾病临床观察[J].湖北中医杂志,2004,26(6)：11-12.
[60]钱秋海.活血化瘀防治糖尿病及并发症机制探讨[J].山东中医杂志,2002,21(3)：131-133.
[61]郑国静,常瑜,程益春.糖尿病肾病的中医治疗思路和方法[J].湖北中医杂志,2004,26(1)：23-24.
[62]李大钧,范克.糖尿病肾病的中医辨证治疗[J].河北中医,2001,23(9)：682-683.
[63]谢宗昌.糖尿病性肾病辨证施治心得[J].浙江中医杂志,2003,38(3)：128-129.
[64]王改勤,姚丽,张寒梅.辨证治疗糖尿病肾病体会[J].江西中医药,2004,38(5)：49.
[65]边芳,赵佩民,张志深,等.中西医结合治疗早期糖尿病肾病的临床观察[J].中国中西医结合杂志,2000,20(5)：335-337.
[66]潘海洋,陈琴.中西医结合治疗糖尿病肾病32例疗效观察[J].山西中医,2002,18(4)：31-32.
[67]魏军平.中药糖微康治疗糖尿病肾病的机制研究.北京中医药大学2004,硕士学位论文.
[68]杨广智.化瘀固肾散治疗糖尿病早期肾病94例临床观察[J].山西中医,2003,19(6)：14-15.
[69]周旭生.加减藿朴夏苓汤治疗糖尿病肾病32例[J].吉林中医药,2003,23(2)：16.
[70]魏玲玲.益气活血法治疗早期糖尿病肾病30例临床观察[J].中医杂志,2004,41(1)：39-40.
[71]张志忠.健脾舒肾汤治疗糖尿病肾病临床观察[J].湖北中医杂志,2004,26(6)：20.
[72]贺学林,章素云,陈以平,等.牛蒡子防治STZ糖尿病大鼠早期肾脏病变的实验研究[J].浙江中医杂志,2003,38(2)：88-90.
[73]唐红,徐蓉娟,李红,等.治糖保肾冲剂治疗早期糖尿病肾病的机理研究[J].上海中医药杂志,2002,36(4)：27-29.
[74]廖璞 王淑琴 廖雪松.银杏叶提取物对糖尿病大鼠肾脏保护作用的实验研究[J].中国药房2000,11(3).
[75]南一,南征,姜良铎.益肾通络解毒汤对糖尿病肾病大鼠肾脏功能的影响[J].吉林中医药2007,27(12).
[76]吴以岭,魏聪,贾振华,等.通肾络胶囊对糖尿病肾病大鼠肾脏蛋白激酶C通路及细胞外基质成分的影响[J].中华中医药学刊2008,02.
[77]韩永斌,徐筱玮,张德宪.糖肾平干预糖尿病肾病大鼠肾脏组织TGF—β1和FN表达的实验研究[J].光明中医2008,23(5).
[78]刘启华.肾康丸处方优化研究及其对糖尿病肾病大鼠肾皮质转化生长因子β2型受体表达的影响[J].第-军医大学论文学位硕士,
[79]陈胜.黄芪调节自发糖尿病肾病鼠层粘连蛋白表达的实验研究[J].现代生物医学进展2008,8(7).
[80]陈应强,曾家顺,李龙.黄芪对糖尿病大鼠肾组织NF-κB和MCP-1表达的影响[J]贵州医药2009,33(2).
[81]张丽芬,杨敏,赵进喜,等.黄芪卫矛合剂对糖尿病肾病大鼠尿蛋白的影响[J].中国中药杂志2008,33(2).
[82]杨敏,张丽芬,赵进喜,等.黄芪卫矛合剂对糖尿病肾病大鼠肾组织NO和ET含量影响.实用中医内科杂志.2006,20(6).
[83]苏宁,罗荣敬,苏杭,等.罗惠黄芩苷对糖尿病肾病大鼠肾功能及其抗氧化应激作用的研究[J].中药新药与临床药理.2007,18(5).
[84]郭登洲,王月华,边东等.活血化瘀消癥通络中药对糖尿病肾病大鼠肾组织血管紧张素转化酶相关羧肽酶表达的影响[J].中国全科医学2008,11(5A).
[85]宁勇,刘晓城.姜黄素对糖尿病肾病模型大鼠的防治作用[J].山东中医杂志2004,23(6).
[86]彭月芹,孔祥芬,胡宝峰,等.芪蛭消癓胶囊对糖尿病肾病大鼠肾损害的防治作 用研究[J].河南中医2008,28(5).
[87]Valmadrid CT,Klein R,Moss SE,et al.The risk of cardiovascular disease mortality associated with microalbuminuria and gross protenuria in persons with older-onset diabetes mellitus.Arch Intern Med,2000,160:1093-1100.
[88]张建国.糖尿病肾病早期诊治新进展.华南国防医学杂志,2006,20(2)：30-33.
[89]向红丁.糖尿病肾脏病变.国外医学内分泌学分册,2004,24(2)：125-136.
[90]Wu AY, Kong NC, de Leon FA, Pan CY, Tai TY, Yeung VT, et al. An alarmingly high Prev-alence of diabetic nephropathy in Asian type 2 diabetic patients:the MicroAlbuminuria Prevalenc-e (MAP) Study. Diabetologia 2005,48 (1):17-26.
[91]李红.糖尿病微血管病变发病机制和治疗靶点.浙江大学学报,2006,35(3)：232-237.
[92].Yamagishi S, TakeuchiM, Inagaki Y, et al. Role of advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic microangiopathy [J]. Int J Clin Pharmacol Res,2003,23(4):129-134.
[93]Ong ACM,Fine LG,Am J Kidney Dis,1994;23:2057-
[94]李保春,王林辉,梅小斌.糖尿病性肾病(M).上海.第二军医大学出版社,2005.
[95]SuzukiD, ToyodaM, YamamotoN, eta.l Relationship between the expression of advanced glycation end-products (AGE) and the receptor for AGE (RAGE) mRNA in diabetic nephropathy. InternMed 2006,45:435-441.
[96]Jensen LJ, Denner L, Schrijvers BF, et a.l Renal effects of a neutralizing RAGE-antibody in long-term streptozotocin-diabetic mice. JEndocrinol 2006,188: 493-501.
[97]Inoguchi T,Yu HY,Menne J,et al.Altered gap junction activity in cardiovascular tissues of diabetes.Med Electron Microse,2001,34(2):86-91.
[98]Dunlop M.Aldose reductase and the role of the polyol pathway in diabetic nephropathy.Kidney Int,2000,Suppl 77:3-12.
[99]Scocottarp V,Canz MB,Weiss MF.AGEs induce oxidative stress and activity protein kinase C-betaⅡ in neonatal mesangial cells.Am J Physiol,2000,278(4):676.
[100]Asunare K,Kahno M,Kano H,et al.Possible involvement of phospholipase and by protein kinase C in vascular growth induced by elevated glucose concentration. Hypertension,1996,28(2):159-168.
[101]Bradham DM, Igarashi A, Potter RL, et al. Connective tissue growth factor:a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10[J]. J Cell Biol,1991,114(6): 1285.
[102]Frazier K, Williams S, Kothapalli D, et al. Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor[J]. J Invest Dermatol,1996,107(3):404.
[103]Duncan MR, Frazier KS, Abramson S, et al. Connective tissue growth factor mediates transforming growth factor beta-induced collagen synthesis:down-regulation by cAMP[J]. FASEB J.1999,13(13):1774.
[104]Kothapalli D, Grotendorst GR. CTGF modulates cell cycle progression in cAMP-arrested NRK fibroblasts[J]. J Cell Physiol,2000,182(1):119.
[105]Twigg SM, Joly AH, Chen MM, et al. Connective tissue growth factor/IGF-binding protein-related protein-2 is a mediator in the induction of fibronectin by advanced glycosylation endproducts in human dermal fibroblasts[J] Endocrinology,2002,143(4):1260.
[106]Shi-wen X, Pennington D, Holmes A, et al. Autocrine overexpression of CTGF maintains fibrosis:RDA analysis of fibrosis genes in systemic sclerosis[J]. Exp Cell Res,2000,259(1):213.
[107]Grotendorst GR, Okochi H, Hayashi N. A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene[J]. Cell Growth Differ,1996,7(4):469.
[108]Chen CC, Chen N, Lau LF. The angiogenic factors Cyr61 and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts[J]. J Biol Chem,2001,276(13):10443.
[109]Fan WH, Pech M, Karnovsky MJ. Connective tissue growth factor (CTGF) stimulates vascular smooth muscle cell growth and migration in vitro[J]. Eur J Cell Biol,2000,79(12):915.
[110]Shimo T, Nakanishi T, Kimura Y, et al. Inhibition of endogenous expression of connective tissue growth factor by its antisense oligonucleotide and antisense RNA suppresses proliferation and migration of vascular endothelial cells[J]. J Biochem Tokyo,1998,124(1):130.
[111]Babic AM, Chen CC, Lau LF. Fisp12/mouse connective tissue growth factor mediates endothelial cell adhesion and migration through integrin alphavbeta3, promotes endothelial cell survival, and induces angiogenesis in vivo[J]. Mol Cell Biol, 1999,19(4):2958.
[112]Kondo S, Kubota S, Shimo T,et al. Connective tissue growth factor increased by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases[J]. Carcinogenesis,2002,23(5):769.
[113]Nakanishi T, Kimura Y, Tamura T, et al. Cloning of a mRNA preferentially expressed in chondrocytes by differential display PCR from a human chondrocytic cell line that is identical with connective tissue growth factor (CTGF) mRNA[J]. Biochem Biophys Res Commun,1997,234(1):206.
[114]Xu J, Smock SL, Safadi FF, et al. Cloning the full-length cDNA for rat connective tissue growth factor:implications for skeletal development[J]. J Cell Biochem,2000, 77(1):103.
[115]Folger PA, Zekaria D, GrotendotGet al. Transforming growth factor-beta stimulated connective tissue growth factor expression during cornealmyofibroblast differentiation. Invest-OphthalMol Uis Sc,i 2001,42 (11):2534-2541
[116]Wahab NA, Brinkman H, Mason RMet al. Uptake and intracellular transport of the connective tissue growth factor:a potentialmode of action. Biochem J,2001,359 (ptl)89-97
[117]Min Yang, Haichang Huang, Jingzi Liet al. Tyrosine phosphorylation of the LDL receptor-related protein (LRP) and activation of the ERK pathway are required for connective tissue growth factor to potentiate myofibroblast differentiation. FASEBJ, 2004,18 (15):1920-1921
[118]Wahab NA, Mason RM. Connective tissue growth factor and renal diseases:some answers, more questions. CurrOpin NephrolHypertens,2004,13:53-58
[119]ItoY, Bende RJ, OemarBSet al. Expression of connective tissue growth factor in human renal fibrosis. Kidney Int,1998,53 (4):853-861
[120]MurphyM, Godson C, Cannon Set al. Suppression subtractive hybridization identifies high glecose levels as a stimuls for expression of connective tissue growth factor and other genes in human mesangial cells. J Biol Chem,1999,74 (9):5830-5834
[121]Riser BL, Denichilo M, Cortes Pet al. Regulation of connective tissue growth factor activity in cultured ratmesangial cells and its expression experimental diabetic glomerulosclerosis. JAm SocNephro,l 2000,1 (1):25-38
[122]Riser BL, Denichilo M, Cortes Pet al·Regulation of connective tissue growth factor activity in cultured rat mesangial cells and its expression in experimental diabetic glomerulosclerosis·JAmSoc Neprol,2000,11:25
[123]Mason RM, Li X, Wahab NA·High glucose induces the expression of connective tissue growth factor in human mesangial cells·J Am Soc Nephrol,1997,8:624A
[124]Murphy M, Godson C, Cannon Set al·Suppression subtractive hybridization identifies high glucose levels as a stimulus for expression of connective tissue growth factor and other genes in human mesangial cells·J Biol Chem,1999,274:5830
[125]Wang S, Denichlo M, Brubaker Cet al·Connective tissue growth factor in the tubulointerstitial injury of diabetic nephropathy·Kidney Int,2001,60:96
[126]Wahab NA, Yevdokimova N, Weston BSet al·Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy·Biochem J,2001,359:77
[127]Adler SG, Kang SW, Feld Set al·Glomerular mRNAs in human type 1 diabetes: biochemical evidence for miroalbuminuria as a manifestation of diabetic nephropathy·Kidney Int,2001,60:2330
[128]Wahab NA, Weston BS, Robet Tet al·Connective tissue growth factor and regulation of the mesangial cell cycle:role in cellular hypertrophy·J Am Soc Nephrol, 2002,13:2437
[129]Ito Y, Goldschmeding R, Bende RJet al·Kinetics of connective tissue growth factor expression during experimental proliferative glomerulonephritis·J Am Soc Neprol,2001,12:472
[130]黄海长,李惊子,王海燕·结缔组织生长因子诱导肾成纤维细胞转化成肌成纤维细胞。科学通报,2002,47(1)：37
[131]Twigg SM, Chen MM, Joly AHet al·Advanced glycosylation end products up-regulate connective tissue growth factor (insulin-like growth factor-binding protein-related protein-2) in human fibroblasts:a potential mechanism for expansion of extracelluar matrix in diabetic mellitus·Endocrinology,2001,142(5):1760
[132]Twigg SM, Joly AH, Chen MMet al·Connective tissue growth factor/IGF-binding protein-related protein-2 is a mediator in the induction of fibronectin by advanced glycosylation end products in human dermal fibroblasts·Endocrinology,2002,143(4):1 260
[133]Alder SG, KangSW, Feld Set al·Can glomerularmRNAs in type 1 diabetes be used to predict transition from normoalbumunuria to microalbuminuria? Am J Kidney Dis, 2002,40(1):184
[134]Ayer-leliever A, Brigstock D, Lau Let al·Report on the first international workshop on the CCN family of genes·J Clin Pathol,2001,54:105
[135]Igarashi A, Okochi H, Bradham Dm, et al. Regulation of connective tissue growth factor gene expression in human skin fibroblasts and during wound repair[J]. Mol Biol Cell,1993,4(6):637.
[136]Mori T, Kawara S, Shinozaki M, et al. Role and interaction of connective tissue growth factor with transforming growth factorbeta in persistent fibrosis:A mouse fibrosis model[J]. J Cell Physiol,1999,181(1):153.
[137]周勇,朱健,王奕.细胞因子与2型糖尿病及胰岛素抵抗的相关性研究[J].中国医师进修杂志,2006,29(1)：42-44.
[138]王艳军,韩萍,卢丽萍.糖尿病肾病患者体内IL-6, TNF-α及TGF-β检测及临床意义的分析[J].中国免疫学杂志,2002,18(3)：214-216.
[139]Lofgren P,Van Harmelen V,Reynisdottir S,et al.Secretion of tumor necrosis factor-alpha shows a strong relationship to insulin-stimulated glucose transport in human adipose tissue[J].Diabetes,2000,49(4):688-692.
[140]Amore A,Crina P,Mitola S,et al.Nonenzvmatically glycated albumin(Amadori adducts)enhances nitric oxide synthase activity and gene expression in endothelial cells[J].Kidney Int,1997,51 (1):27-35.
[141]栗德林,苑讯.糖肾康对实验性大鼠ET-1、TNF、 IL-6等的影响[J].中医药信 息,2003,20(2)：57-58.
[142]肖常青,梁瑜祯,苏宏业,等.糖尿病人血浆肿瘤坏死因子α变化及其相关因素研究[J].中国糖尿病杂志,2001,6(9)：369-370.
[143]刘震宇,成兴波,蒋晓红,等.血清TNF-a与2型糖尿病肾病的相关性研究[J]南通大学学报200,06.
[144]Abraham DJ, Shiwen X, Black CM, et al. Tumor necrosis factor alpha suppresses the induction of connective tissue growth factor by transforming growth factor-beta in normal and scleroderma fibroblasts[J]. J Biol Chem,2000,275(20):15220.
[145]Dammeier J, Beer HD, Brauchle M, et al. Dexamethasone is a novel potent inducer of connective tissue growth factor expression.Implications for glucocorticoid therapy[J]. J Biol Chem,1998,273(29):18185.
[146]Chambers RC, Leoni P, Blanc-Brude OP, et al. Thrombin is a potent inducer of connective tissue growth factor production via proteolytic activation of protease-activated receptor-l[J].J Biol Chem,2000,275(45):35584.
[147]Schild C,Trueb B.Mechanical stress is required for high-level expression of connective tissue growth factor[J].Exp Cell Res,2002,274(1):83.
[148]Kessler D,Dethlefsen S,Haase I,et al.Fibroblasts in mechanically stressed collagen lattices assume a"synthetic"phenotype[J]JBiol Chem,2001,276(39):36575.
[149]贾汝汉,陈玲.氧化应激在糖尿病肾病发病中的作用(上).中国中西医结合肾病杂志,2006,7(8)：373-375
[150]Maritim AC,SandersRA,Watkins JB. Diabetes, ox-idative stress, and antioxidants: a review. JBiochemMolToxico,1 2003,17:24-38.
[151]BrownleeM.Biochemistry andmolecular cell biology of diabetic comp lications. Nature,2001,414:813-820.
[152]XuY,OsborneBW,StantonRC.DiabetesCauses Inhibition ofGlucose 6-Phosphate Dehydrogenase via Activation of Protein Kinase A which Contributes toOxidative Stress inRatKidneyCortex.Am JPhysiolRenalPhysio,l 2005,289(5):1040-1047.
[153]陈玲,贾汝汉,丁国华,等.缬草油对2型糖尿病大鼠肾脏的保护作用及其机制探讨.中华肾脏病杂志,2003,19(3)：168-172.
[154]AksunAS,Ozmen B,OzmenD,et al.Serum and urinary nitric oxide in Type 2 diabeteswith orwithoutmicroalbuminuria:relation toglomerular hyperfiltration. JDiabetes Complications,2003,17(6):343-348.
[155]Banda N,Nakamura T,MatsumuraM,et al.Possible relationship of monocyte chemoattratant protein-1 with diabetic nephropathy. Kinney In,t 2000,58(2):684-686.
[156]ScivittaroV,GanzMB,WeissMF.AGEs induce oxidative stressand activate protein kinaseC-beta(Ⅱ)in neotalmesangialcells.Am JPhysiol RenalPhysio,l 2000,278 (4): 676-678.
[157]SusztakK,RaffAC, SchifferM, et al.Glucose-induced reactive oxygen species cause apoptosisofpodocytesand podocyte depletion atthe onset ofdiabetic nephropathy. Diabetes,2006,55(1):225-233.
[158]HaH,YuMR, ChoiYJ, et a.l Role of high glucose-induced nuclear factor-kappaB activation in monocyte chemoattractant protein-1 expression by mesangial cells. J Am Soc Nephro,l 2002,13 (4):894-902.
[159]MoriiT, FujitaH,Narita T, et al. Association ofmonocyte chemoat tractantprotein-1 with renal tubulardamage in diabetic nephropathy.J Diabetes Complications, 2003,17(1):11-15.
[160]成宏,陈允硕,巫向前.层粘连蛋白的生物学特性研究现状及应用[J].国外医学·临床生物化学与检验学分册,1995,16(5)：217
[161]Kreisberg JI,Ayo SH.The Glomerular Mesangiumin Diabetes Mellitus [J].Kidney Int,1993,43:109-110
[162]汪洪流.Ⅱ型糖尿病肾病和红细胞膜ATP酶活性的关系.《淮海医药》2001年6月第19卷第3期
[163]Simchons,Gavin JR.Influence of reduced red cell deformability onregional blood flow[J].Am J Phyiol,1987:253,898
[164]丁国宪,陈家伟,何戎华,等.Ⅱ型糖尿病伴高血压机制探讨[J].中华内分泌代谢杂志,1995,4(11)：214
[165]王尧,成必成,腾航,等.糖尿病肾病患者红细胞膜上Na+、K+-ATP酶及Ca2＋、 Mg2+-ATP酶活性的变化[J].南京铁道医学院学报,1998,17(2)：123
[166]卢欣萍,欧阳安,苏天水,等.糖尿病患者红细胞膜钙、镁ATP酶研究[J].中华内分泌代谢杂志,1992,8(3)：155
[167]Maxfield EK,Cameron NE,Cotter MA.Effects of diabetes on reactivity of sciatic vasa nervorum in rat.J Diabetes Compl,1997,11(1):47-55.
[168]刘东方,严中德,沈鼎明,等.糖尿病自主神经病变和糖尿病肾病关系探讨.中国糖尿病杂志,1998,2(1)：6.
[169]Michimata T,Murakami M,Iriuchijima T.Nitric oxide-dependent soluble guanylate cyclase activity is decreased in platelets from male NIDDM patient.Life Sci,1996,59:1463-1471.
[170]Agewall S.Insulin sensitivity and haemostatic factors in men at high and low cardiovascular risk.J Intern Med,1999,246:489-495.
[171]Karamanos B,Porta M,Songini M,et al.Different risk factors of microangiopathy in patients with type 1 diabetes mellitus of short versus long duration:the Eurodiab IDDM Complications Study.Diabetologia,2000,43:348-355.
[172]NeuhoferW, Pittrow D-Role of endothelin and endothelin receptor antagonists in renal disease·Eur J Clin Invest,2006,36 (Surppl3):78-88
[173]Hargrove GM, Dufresne J, Whiteside Cet al. Diabetesmellitus increases endothelin-1 gene transcription in ratkidney. Kidney Int,2000,58 (4):1534-1545
[174]Lopez-Ongil S, Diez-MarquesML, GrieraMet al. Crosstalk betweenmesangialand endothelial cells:angiotensin Ⅱ down-regulates endothelin-converting enzyme 1-Cell PhysiolBiochem,2005,15 (1-4):135-144
[175]KuoHT, Shin SJ, KuoMCet al. Effects of specific endothelin-1 receptor antagonists on proliferation and fibronectin production of glomerularmesangial cells stimulated with Angiotensin Ⅱ·Kaohsiung JMed Sc,i 2006,22 (8):371-376
[176]ItohY, NakaiA, KakizawaHet al. Alteration of endothel in-1 concentration in STZ-induced diabetic ratnephropathy·Effects of a PGI (2) derivative-Horm Res, 2001,56(5-6):165-171
[177]ChenHC, Guh JY, Shin SJet al. Reactive oxygen species enhances endothelin-1 production of diabetic rat glomeruli in vitro and in vivo·JLab ClinMed,2000,135 (4): 300-302
[178]Ak G, Buyukberber S, Sevinc Aet al. The relation between plasma endothelin-1 levels and metabolic contro,l risk fators, treatmentmodalities, and diabetic microangiopathy in patients with Type 2 diabetes mellitus-J Diabetes Complications, 2001,15 (3):150-157
[179]Bruno CM,Meli S,MarcinnoMet al.Plasma endothelin-1 levels and albumin excretion rate in normotensive, microalbuminuric type 2 diabetic patients-J Biol Regul HomeostAgents,2002,16 (2):114-117
[180]叶山东.内皮素和糖尿病肾脏病变.国外医学·泌尿系统分册,1997,17(1)：35-37
[181]陈明,黄颂敏.内皮素、-氧化氮与糖尿病肾病[J].国外医学内分泌学分册,1999,2(19)：89-72.
[182]Zhang W,Khanna P,Chan LL,et al.Diabetes induced apoptosis in rat kidney[J].Biochem Mol Med,1997,61(1):58-62.
[183]Sugiyama H,Kashihara N,Makino H,et al.Apoptosis in glomerular sclerosis [J].Kidney Int,1996,49(1):103-111.
[184]Ortriz A,Ziyadeh FN,Neilson EG.Expression of apoptosis-regulatory gene in renal proximal tubular epithelial cells exposed to high ambient glucose and in diabetic kidneys.JInvest Med,1997,45(2):50-56.
[185]Uda S,Yoshimura A,Sugenoya Y,et al.Mesangial proliferative nephritis in man is associated with increased expression of the cell srrvival factor,bcl-2.Am J Neprol,1998,18:291-295.
[186]康健,羊惠君,李爱冬.糖尿病早期大鼠肾小管上皮细胞凋亡与增殖的观察.川北医学院学报,1999,14(2)：4-6.
[187]Harrison DJ.Cell death in the diseased glomerulus.Histopathology,1988, 12:679-683.
[188]Shimizu A,Kitamura H,Masuda Y,et al.Apoptosis in the repair process of experimental proliferative glomerulonephritis.Kidney Int,1995,47:114-121.
[189]Sugiyama H,Kashihara N,Makino H,et al.Apoptosis in glomerular sclera-sis.Kidney Int,1996,49:103-111.
[190]Shimizu A,Masuda Y,Kitamura H,et al.Apoptosis in progressive crescentic glomerulonephritis. Lab Invest,1996,74:941-951.
[191]Gauer S,Yao J,Schoedklmann HO,et al.Adhesion molecules in the glomerular mesangi um.Kidney Int,1997,51:1447-1153.
[192]Kitamura M and Ishikawa Y.Three-dimensional matrix primes mesangial cells to downregulation of alpha smooth muscle actin via deactivatiom of GArG box elements.Kidney Int,1998,53:690-697.
[193]Sugiyama H,Kashihara N,Maeshima Y,et al.Regulation of survival and death of mesangial cells by extracellular matrix.Kidney Int,1998,54:1188-1196.
[194]Johnson RJ,Floege J,Yoshimura A,et al.The activated mesangial cell:a glomertular myofibroblast? J Am Soc Nephrol,1992,2:190-197.
[195]White E.Life,death,and the pursuit of apoptosis[J].Genes Dev,1996,10(1):1-15.
[196]Korsmeyer SJ.Bcl-2 gene family and the regulation of programmed cell death [J].Cancer Res,1999,59(7 Suppl):1693s-1700s.
[197]张艳玲,段惠军,李春香,等.糖尿病大鼠肾脏细胞凋亡与Bax和Bcl-2基因表达[J].中国糖尿病杂志,2002,10(3)：159-162.
[198]Yang B,Jonnson TS,Thoamas GL,et al.Expression of apoptosisrelated genes and proteins in experimental chronic renal scarring [J].J Am Soc Nephrol,2001,12(2): 275-288.
[199]Gobé GC,Zhang XJ.Relationship between expression of Bcl-2 genes and growth factors in ischemic acute renal failure in the rat [J] J Am Soc Nephrol,2000, 11(3):454-467.
[200]苏君梅,董峰,易华,等.糖尿病大鼠肾脏细胞凋亡的研究[J].武汉大学学报(医学版),2003,24(1)：17-20.
[201]张新爽,刘亚玲,张艳玲.苯那普利对糖尿病大鼠肾脏细胞凋亡及Fas和Fas-L表达的影响[J].河北医药,2003,25(4)：243-245.
[202]段惠军,张艳玲,史永红,等.苯那普利对糖尿病大鼠肾脏细胞凋亡的影响[J].药学学报,2002,37(6)：409-411.
[203]赵玲,顾江萍,贾德林,等.细胞凋亡与糖尿病肾病的关系及糖肾康作用机制的研究[J].中国中西医结合肾病杂志,2003,4
[204]Mogensen CE.Mieralbuminuria as apredietor of clinieal diabetie nePhOPathy kidney Int,1987:67-75
[205]王吉耀.内科学(下册),北京：人民卫生出版社,2005,第-版：981
[206]张蕙芬,迟家敏,王瑞萍.实用糖尿病学,北京：北京：人民卫生出版社,2004,第二版：364-365
[207]张秀珍,李素.内分泌代谢疾病与肾脏,上海：复旦大学出版社,2004,第-版：115-116
[208]王晓光,姚源漳.肾脏病诊断与治疗,北京：人民军医出版社,2006,第-版：105-106
[209]KozlowskaL, Rosolowska-HuszczD, RydzewskiA·[J]·Nephrology (Carlton),2004, 9 (5):319-324(?)
[210]HansenHP, Tauber-Lassen E, Jensen BR, et al·[J]·Kidney Int,2002,62(1): 220-228(?)
[211]MitchWE·[J]·Kidney Int,2005,4(94):S133-135(?)
[212]Feiten SF,Draibe SA,Watanabe R, et al·[J]·Eur J Clin Nutr,2005,59(1):129-136(?)
[213]American Diabetes Association·[J]·Diabetes Care,2004,27(Suppll):S79-83(?)
[214]Diabetes Control and Complications Trial-Epidemi-ology of Diabetes Interventions and Complications Research Group.[J].JAMA,2003,290 (16):2159-2167(?)
[215]Sarafidis PA,Lasaridis AN,Nilsson PM,et al.[J].Am J Hypertens,2005,18 (2 Pt 1): 227-234(?)
[216]ParvingHH, LehnertH, Brochner-Mortensen J, et al.[J].N Engl JMed,2001, 345(12):870-878(?)
[217]Lewis EJ,HunsickerLG,ClarkeWR,et al.[J].N Engl JMed,2001,345(12):851-860(?)
[218]RemiuzziG, RuggenentiP, PernaA,et al.[J].J Am Soc Nephro,l 2004,15(12): 3117-3125(?)
[219]BarnettAH, Bain SC, BouterP, etal·[J]·N Engl JMed,2004,351(19):1952-1961(?)
[220]Mogensen CE,Neldam S,Tikkanen I,et al·[J]·BMJ,2000,321(7274):1440-1444(?)
[221]American Diabetes Association·[J]·DiabetesCare,2005,28(Suppll):S4-S36(?)
[222]Moriyama T,Oka K,Ueda H,et al·[J]·Clin Exp Nephro,l 2004,8(3):230-236(?)
[223]RuggenentiP,FassiA,Ilieva AP, et al·[J]·N Engl JMed,2004,351(19):1941-1951(?)
[224]RachmaniR,Slavachevsky I,AmitM, etal·[J]·DiabeticMed,2004,21(5):471-475(?)
[225]Shah S,Paparello J,Danesh FR·[J]·AdvChronic KidneyDis,2005,12(2):187-195(?)
[226]Thallas-Bonke V,Lindschau C,Rizkalla,et al·[J]·Diabetes,2004,53(11): 2921-2930.
[227]Alderson NL,Chachich ME,Frizzell N,et al·[J].Diabetologia,2004,47(8): 1385-1395.
[228]LalMA,BrismarH,EklofAC,et al·[J]-Kidney Int,2002,61(6):2006-2014-
[229]ArticoM,De Santis S,TranquilliLealiFM, et al·[J]·JDiabetes Complications,2004, 18(2):119-125.
[230]Tohma T,ShimabukuroM,OshiroY,et al-[J]·Metabolism,2004,53(11):1405-1410
[231]Mankhey RW,Bhatti F,Maric C·[J]·Am J PhysiolRenalPhysiol.2005,288(2): F399-405.
[232]叶跃红,高科,李兴禄.尿沉渣分析和尿微量白蛋白在早期糖尿病肾病中的临床应用[J].重庆医学,2003,32(12)：1642.
[233]邓晓初.尿白蛋白／肌酐比值检测法在早期2型糖尿病肾病中的应用[J].重庆医学,2005,34(1)：46.
[234]Kanauchi M,Dohi K.Predictorsof diabetic renal lesions in type 2 diabetes associated with microalbuminuria.Eur J Clin Invest,2001,31 (2):110.
[235]Lenley KV,Abolillah I,MyersBD,et al.Evolution of incipient nephropathy in type 2 diabetesmellitus.Kidney Int,2000,58 (3):1228.
[236]王艳萍等.NAG及β2-微球蛋白联合检测对糖尿病肾病早期诊断的意义[J]中国医科大学学报2004,(33)1.
[237]刘振平,张艳玲,陆菊明·糖尿病肾病的标记物[J].中华肾脏病杂志,1999,15(6)：389-391.
[238]陈澍,刘雪芳.链脲佐菌素诱导大鼠糖尿病肾病模型的建立[J].实用医学杂志,2006,22(11)：1239-1240.
[239]宋恩峰等.2型糖尿病肾病大鼠模型制备研究实用医学杂志2007,23(18)
[240]高苹.2型糖尿病肾病大鼠模型的建立.中国中西医结合肾病杂志2007,8(6).
[241]杨钱红.贝那普利对糖尿病肾病患者尿微量白蛋白的影响。吉林医学,Jilin Medical Journal,编辑部邮箱2010年04期
[242]Lewei EJ,Hunsieker LG,Bain Rp,etal.The efeet of angiotensin converting enzyme inhibition on diabetie nePhorPathy.The Collaborative Study GoruP.N Eng J Med,1993, 329:1456-1462.
[243]Rveid M,Savin HJutrin I,etal.Long-term stabilizing efeet of angiotensin Converting enzyme inhibition on Plasma ereatinine and on Porteinuriain Nomrotensive tyPe Ⅱ diabetie Patients,Ann IntenrMed,1993,118:577-581.
[244]Heart outeomes Prevention Evaluation (HOPE)Study Investigators. Effeets of ramiPril on aeluiovaseular and mieorvaseular outeomes in PeoPle with diabetes mellitus:results of the HOPE Study and MICRO-HOPE Substudy Laneet,2000,355: 253-259
[245]王苏杭.血管紧张素转换酶抑制剂和血管紧张素受体拮抗剂治疗糖尿病肾病的新进展,安徽医药,2005,9(5)：356-355.
[246]邹敏书刘雪梅余健轰国明。贝那普利和维生素E对糖尿病肾病大鼠氧化应激的影响。中目药师2的7年第10卷第6期Pharmaeis,,vol.1ONo.6
[247]赵进喜,邓德强,李靖.糖尿病肾病相关中医病名考辨,南京中医药大学学报(自然科学版),2005,21(5)：288-289.
[248]清·张秉成.《成方便读·卷之-》.上海科技出版社,1963：9.
[249]明·张锡纯.《医学衷中参西录》.中国文史出版社,北京,2003：34.6
[250]清·吴仪洛.《本草从新》.大津科技出版社,天津.2003：43.
[251]清·黄宫绣.《本草求真》.上海科技出版社,上海,195.9
[252]明·张锡纯.《医学衷中参西录》.中国文史出版社,北京,2003：350.
[253]中药大词典.上海科学技术出版社,1993第三版上册,166-16.8
[254]中药大词典.上海科学技术出版社,1993第二版上册,1127-113.0
[255]中药人词典.上海科学技术出版社,1993第止版下册,1596-159.9
[256]中药大词典.上海科学技术出版社,1993第二版上册,517-51.9
[257]雷载权等.《中药学》第六版.上海科技出版社.1999,90-325.
[258]陈力真等.地黄多糖b对荷肉瘤180例小鼠T淋巴细胞的作用.中国药理学报,1995,16(4)：337.
[259]石君华.黄芪对实验性MD人鼠肾脏保护作用的实验研究.[J]中国中医药科技,2000,6(5)：314.
[260]马子密,傅延龄土编.历代本草药性汇解.中国医药科技出版社,2002第-版,214-219.
[261]范幼箔.当归改善老年糖尿病肾病功能的研究.[J]中国老年杂志,1996,16：77.
[262]董柯等.水蛭对系膜增殖性肾炎蛋白尿、脂质代谢及凝血机制的影响.中华内科杂志,1995,34(4)：250.
[263]马子密,傅延龄土编.历代本草药性汇解.中国医药科技出版社,2002第-版,5-5.
[264]Gilbert RE, Akdeniz A,Weitz S, et a.l Urinary connective tissue growth factor excretion in patientswith type 1 diabetes and nephropathy.DiabetesCare,2003,26: 2632-2636.
[265]Mason RM,Wahab NA. Extracellular matrix metabolism in diabetic nephropathy. JAm SocNephro,1 2003,14:1358-1373.
[266]Hashimoto G, Inoki I, FujiiY, et a.l Matrixmetalloproteinases cleave connective tissue growth factor and reactivate angiogenic activity of vascular endothelial growth factor165. J BiolChem,2002,277:36288-36295.
[267]Twigg SM,CooperME.The time has come to target connective tissue growth factor in diabetic com-plications.Diabetologia,2004,47:965-968.
[268]Mclennan SV,WangXY,MorenoV, et a.l Connective Tissue Growth Factor MediatesHigh Glucose Effects on Matrix Degradation through Tissue Inhibitor ofMatrixMetalloproteinase Type 1:Implications for Diabetic Nephropathy. Endocrin-ology,2004,145:5646-5655.
[269]Twigg SM,CaoZ, SVMC, eta.l Renal connective tissue growth factor induction in experimental diabetes is prevented by aminoguanidine.Endocrinology,2002,143: 4907-4915.
[270]Andersen S, van Nieuwenhoven FA,Tarnow L, et a.l Reduction of urinary conn-ective tissue growth factor by Losartan in type 1 patients with diabetic nephro-pathy.Kidney Int,2005,67:2325-2329.
[271]涂晓文.结缔组织生长因子：糖尿病肾病治疗的新靶点.国际泌尿系统杂志2006,26(1).