川芎嗪联合贝那普利对GK大鼠肾间质病变炎症因子和蛋白激酶C的表达水平影响的实验研究
|
摘要
目的：初步观察川芎嗪联合贝那普利对GK大鼠并发肾病的大鼠肾组织TGFβ1,MCP-1、TGFβ1 mRNA、PKC活性、PKCβ等表达水平的影响及其调控作用的可能机制；探讨DN病变程度与信号传导及细胞因子表达的关系,并进一步探讨探讨川芎嗪对糖尿病肾病肾小球硬化及肾间质纤维化的保护作用和防治机制,寻找早期治疗DN病变的中医药新方法。
方法：将40只雄性GK大鼠随机分为模型组、贝那普利组、川芎嗪组、川芎嗪+贝那普利组；每组10只。模型组,按5ml·kg-1·d-1灌服生理盐水；贝那普利组,按1.6mg·kg-1·d-1灌服贝那普利悬液；川芎嗪组,按150mg·kg-1·d-1灌胃(其浓度为20mg/ml)；川芎嗪+贝那普利组；另设10只同周龄WISTER大鼠作为(空白对照组),共五组动物。川芎嗪按150mg·kg-1·d-1灌服,加灌贝那普利悬液(按1.6mg·kg-1·d-1)；共16周。实验第8周、第12周和第16周将大鼠放入代谢笼中,收集24h尿液,测定24h尿蛋白定量；治疗16周后,将大鼠用3%戊巴比妥钠腹腔麻醉后剖腹,摘取肾脏。反转录聚合酶链反应法(RT-PCR)测肾组织TGFβ1 mRNA含量,免疫组化检测肾脏MCP-1,TGFβ1和PKCβⅠ、PKCβⅡ的表达,并用[3H]PDBu结合法测定肾皮质的PKC的活性,同时测定各组大鼠体重、血糖、血脂、Scr、BUN及Ccr变化。
结果：与其它组比较,模型组大鼠血糖明显增高(P<0.05),24h尿蛋白定量明显升高(P<0.05),24h尿蛋白等指标增加(P<0.05,或p<0.01)。免疫组化及RT-PCR显示模型组大鼠肾组织MCP-1、TGFβ1、TGFβ1 mRNA表达明显增加(P<0.05,或p<0.01)；模型组和治疗各组PKCm活性均较正常组明显升高(p<0.05),而PKCc活性较正常组明显降低(p<0.05)。治疗各组PKCm活性较模型组明显降低(p<0.05),PKCc活性较模型组明显升高(p<0.05)。治疗各组组间比较,PKCm活性和PKCc活性均无统计学差异(p>0.05)。模型组肾小球内PKCβⅠ表达明显高于正常组(P<0.01)：治疗组肾小球内PKCβⅠ表达明显低于DM组(P<0.01),治疗组组间肾小球内PKCβⅡ表达无明显差异(P>0.05)。
结论：川芎嗪联合贝那普利能降低糖尿病血糖、TG和TC；下调肾组织TGFβ1、MCP-1、TGFβ1 mRNA表达水平,降低血清肌酐、尿素氮水平,提高内生肌酐清除率,减少尿白蛋白的排泄,改善肾组织炎症病变和抗凝作用,从而改善DN大鼠的肾功能。抑制肾皮质中PKC转位激活及PKCβⅠ、PKCβⅡ亚型的表达,抑制细胞外基质蓄积。川芎嗪联合贝那普利对实验性糖尿病大鼠具有肾保护作用,其作用机制与其抑制肾皮质PKC激活和抑制PKCβ亚型的表达和降低肾组织TGFβ1、MCP-1水平有关。
Objective: To observe ligustrazine combined with benazepil tablets _prevention and cure in expression level of TGFβ1、MCP-1、TGFβ1mRNA in GK rats nephridial tissue tentatively and influences renal protein kinase C(PKC) activity and expression of PKCβisofoims in diabetic rat. To evalute the possible mechanisms of effects on diabetic neuropathy (DN) on earlier period. To probe into the connection between diabetic neuropathy and inflammatory to open out the possible mechanisms of DN for appraising and diagnosing new quideline on diabetic neuropathy on earlier period.
Methods:Forty GK male rats were randomly divided into four groups:10 every groups, respectively for model group, ligustrazine group, benazepil group and ligustrazine combined with benazepil group. Drench with NS 5ml·kg-1·d-1、benazepill.6mg·kg-1·d-1、ligustrazine 150mg·kg-1·d-1、ligustrazine combined with benazepil (150mg·kg-1·d-1+1.6mg·kg-1·d-1) to rats respectively, according to the group in 16 weeks. Puting big mouses into metabolism cages in the 8th week, the 12th week and the 16th week, collecting urine to determine quantitation of Urine protein in 24 hours. Treat for 16 weeks, anaesthetize the big mouse by 3% pentobarbital,then cut open the belly of rats and pick its kidney, The mRNA levels of TGF-β1 in renal cortex were measured by reverse transcription polymerase chain reaction(RT-PCR),examine TGF-β1、MCP-1 content in renal organize by means of by means of immunohistochemistry, The PKC activity was measured by[3H] phorbol 12,13-dibutyrate([3H] PDBu) binding assay. The expression of PKCI andⅡisoforms in glomerulus was assessed by immunohistochemistry.
Result:Compared with other group, the blood glucose of model group rats increase obviously (P<0.05), quantitation of 24h Urine protein rise obviously (P<0.05), degrade the express level of TGF-β1、MCP-1、TGFβ1mRNA and CPKβin renal organizes increase obviously (P<0.05,或p<0.01); ligustrazine combined with benazepil tablets can protect the kidney for lowerring blood glucose、TG and TC, degrading TGFβ-1、MCP-1、TGFβ1 mRNA express level in renal organize, decreasing serum albumin、blaood urea mitrogen and increasing creatinine clearance,at the same time, reducing Urine protein level.[3H] PDBu binding assay of group model showed a significant increase in memberane associated protein Icinase C (mPKC) activity and a significant decrease in cytosol associated protein kinase C (cPKC) activity in venal cortex compared with group normal(P<0.01); control group showed asignificant increase in cPKC activity and a significant decrease in mPKC activity compared with group DM (P<0.01); No significant difference was found between control group in renal cortical PKC activity (P>0.05). Immunohistochemistry showed a significant increase in PKCβ1 expression in glomerulus in group model,compared with in control group (P<0.01); PKCβⅠexpression in glomerulus in control group was significantly lower than in group model (P<0.01).The control group showed nodifference in glomemlar expression of PKCβⅠand renal cortical expression of PKCβⅠand CPKβⅡisoforms (P>0.05).
Conclusion:ligustrazine combined with benazepil can reduce great mouse blood glucose level of diabetic rats and improve nephric tubule pathological change, moreover; it can play its roles depend on resisting inflammation and anticoagulatory function.One of the possible mechanisms of DN is to degrade TGF-β1、MCP-1 and TGFβ1mRNA and at least partially via the inhibition of PKC activation and PKCβisoform expression in renal cortex.
方法：将40只雄性GK大鼠随机分为模型组、贝那普利组、川芎嗪组、川芎嗪+贝那普利组；每组10只。模型组,按5ml·kg-1·d-1灌服生理盐水；贝那普利组,按1.6mg·kg-1·d-1灌服贝那普利悬液；川芎嗪组,按150mg·kg-1·d-1灌胃(其浓度为20mg/ml)；川芎嗪+贝那普利组；另设10只同周龄WISTER大鼠作为(空白对照组),共五组动物。川芎嗪按150mg·kg-1·d-1灌服,加灌贝那普利悬液(按1.6mg·kg-1·d-1)；共16周。实验第8周、第12周和第16周将大鼠放入代谢笼中,收集24h尿液,测定24h尿蛋白定量；治疗16周后,将大鼠用3%戊巴比妥钠腹腔麻醉后剖腹,摘取肾脏。反转录聚合酶链反应法(RT-PCR)测肾组织TGFβ1 mRNA含量,免疫组化检测肾脏MCP-1,TGFβ1和PKCβⅠ、PKCβⅡ的表达,并用[3H]PDBu结合法测定肾皮质的PKC的活性,同时测定各组大鼠体重、血糖、血脂、Scr、BUN及Ccr变化。
结果：与其它组比较,模型组大鼠血糖明显增高(P<0.05),24h尿蛋白定量明显升高(P<0.05),24h尿蛋白等指标增加(P<0.05,或p<0.01)。免疫组化及RT-PCR显示模型组大鼠肾组织MCP-1、TGFβ1、TGFβ1 mRNA表达明显增加(P<0.05,或p<0.01)；模型组和治疗各组PKCm活性均较正常组明显升高(p<0.05),而PKCc活性较正常组明显降低(p<0.05)。治疗各组PKCm活性较模型组明显降低(p<0.05),PKCc活性较模型组明显升高(p<0.05)。治疗各组组间比较,PKCm活性和PKCc活性均无统计学差异(p>0.05)。模型组肾小球内PKCβⅠ表达明显高于正常组(P<0.01)：治疗组肾小球内PKCβⅠ表达明显低于DM组(P<0.01),治疗组组间肾小球内PKCβⅡ表达无明显差异(P>0.05)。
结论：川芎嗪联合贝那普利能降低糖尿病血糖、TG和TC；下调肾组织TGFβ1、MCP-1、TGFβ1 mRNA表达水平,降低血清肌酐、尿素氮水平,提高内生肌酐清除率,减少尿白蛋白的排泄,改善肾组织炎症病变和抗凝作用,从而改善DN大鼠的肾功能。抑制肾皮质中PKC转位激活及PKCβⅠ、PKCβⅡ亚型的表达,抑制细胞外基质蓄积。川芎嗪联合贝那普利对实验性糖尿病大鼠具有肾保护作用,其作用机制与其抑制肾皮质PKC激活和抑制PKCβ亚型的表达和降低肾组织TGFβ1、MCP-1水平有关。
Objective: To observe ligustrazine combined with benazepil tablets _prevention and cure in expression level of TGFβ1、MCP-1、TGFβ1mRNA in GK rats nephridial tissue tentatively and influences renal protein kinase C(PKC) activity and expression of PKCβisofoims in diabetic rat. To evalute the possible mechanisms of effects on diabetic neuropathy (DN) on earlier period. To probe into the connection between diabetic neuropathy and inflammatory to open out the possible mechanisms of DN for appraising and diagnosing new quideline on diabetic neuropathy on earlier period.
Methods:Forty GK male rats were randomly divided into four groups:10 every groups, respectively for model group, ligustrazine group, benazepil group and ligustrazine combined with benazepil group. Drench with NS 5ml·kg-1·d-1、benazepill.6mg·kg-1·d-1、ligustrazine 150mg·kg-1·d-1、ligustrazine combined with benazepil (150mg·kg-1·d-1+1.6mg·kg-1·d-1) to rats respectively, according to the group in 16 weeks. Puting big mouses into metabolism cages in the 8th week, the 12th week and the 16th week, collecting urine to determine quantitation of Urine protein in 24 hours. Treat for 16 weeks, anaesthetize the big mouse by 3% pentobarbital,then cut open the belly of rats and pick its kidney, The mRNA levels of TGF-β1 in renal cortex were measured by reverse transcription polymerase chain reaction(RT-PCR),examine TGF-β1、MCP-1 content in renal organize by means of by means of immunohistochemistry, The PKC activity was measured by[3H] phorbol 12,13-dibutyrate([3H] PDBu) binding assay. The expression of PKCI andⅡisoforms in glomerulus was assessed by immunohistochemistry.
Result:Compared with other group, the blood glucose of model group rats increase obviously (P<0.05), quantitation of 24h Urine protein rise obviously (P<0.05), degrade the express level of TGF-β1、MCP-1、TGFβ1mRNA and CPKβin renal organizes increase obviously (P<0.05,或p<0.01); ligustrazine combined with benazepil tablets can protect the kidney for lowerring blood glucose、TG and TC, degrading TGFβ-1、MCP-1、TGFβ1 mRNA express level in renal organize, decreasing serum albumin、blaood urea mitrogen and increasing creatinine clearance,at the same time, reducing Urine protein level.[3H] PDBu binding assay of group model showed a significant increase in memberane associated protein Icinase C (mPKC) activity and a significant decrease in cytosol associated protein kinase C (cPKC) activity in venal cortex compared with group normal(P<0.01); control group showed asignificant increase in cPKC activity and a significant decrease in mPKC activity compared with group DM (P<0.01); No significant difference was found between control group in renal cortical PKC activity (P>0.05). Immunohistochemistry showed a significant increase in PKCβ1 expression in glomerulus in group model,compared with in control group (P<0.01); PKCβⅠexpression in glomerulus in control group was significantly lower than in group model (P<0.01).The control group showed nodifference in glomemlar expression of PKCβⅠand renal cortical expression of PKCβⅠand CPKβⅡisoforms (P>0.05).
Conclusion:ligustrazine combined with benazepil can reduce great mouse blood glucose level of diabetic rats and improve nephric tubule pathological change, moreover; it can play its roles depend on resisting inflammation and anticoagulatory function.One of the possible mechanisms of DN is to degrade TGF-β1、MCP-1 and TGFβ1mRNA and at least partially via the inhibition of PKC activation and PKCβisoform expression in renal cortex.
引文
[1]姚建,陈明道,糖尿病肾病极其早期防治。中华内分泌代谢杂志；2002,18：330-331
[2]Li Ls.End-stage renal disease in China. [J]. Kidney Int,1996,49:287.
[3]Raij L. Recommendation for the management of special populations: renal disease in diabetes. Am J Hypertens,2003,16:46-49
[4]佟之复,李宁华,苗俊梅等.2型糖尿病肾病流行病学研究进展[J].中国老年学杂志,2001,21(3)：241-243.
[5]Brownlee M, Cerami Vlassara H, et al. Advanced glycosylation end products
in tissue and the biochemical basis of diabetic complications. N Engl J Med,1988,318:1315
[6]刘志红,黎磊石.榕尿病肾病发病机理.中华肾脏病杂志,1999,15(2)：121
[7]朱禧星.现代搪尿病学.第1版上海：上海医科大学出版社,2000；319
[8]吴永贵,林辉,钱浩,等.灯盏花素对大鼠糖尿病模型肾组织TGFβ1与CTGF表达影响的实验研究.中国药理学通报,2004；20(9)：1050-4
[9]Phillip sAO, Steadman R, Diabetic nephropathy:the central role of renal proximal tubular cells in tubulointerstitial injury. Histol Histopathol, 2002,17(1):247-252
[10]苏宁,罗容敬,邝枣园,等TGF—β1对糖尿病肾病早期ECM沉积影响的实验研究[J].中国实用医药,2007,11(2)：57-59
[11]Haneda M, Koya D, Kikkawa R. Cellular mechanisms in the development and progression of diabetic nephropathy:activation of the DAG-PKC-ERK pathway. Am J Kidney Dis.2001:38(4 Suppl 1):S178-81
[12]Ways DK, Sheetz MJ. The role of proteinof the complications of diabetes. Vitamkinase C in the developmentHorm.2000:60:149-93
[13]Koya D, Kikkawa R, Kashiwagi A, et al. Activation of Protein Kinase C-Mitogen Activated Protein Kinase Pathway and Diabetic Nephropathy. CIN'2003'3th congress of nephropathy in Internet. http://www.unmet.edu/cin2003/conf/koya/koya html
[14]Sheetz MJ,King GL.Molecular under-standing of hyperglycemia's adverse effects for diabetic complications. JAMA.2002:288:2579-88.
[15]Babazono T, Kapor-Drezgic J, Dlugosz JA, et al. Altered expression andsubcellular localization of diacylglycerol-sensitive protein kinase C isoforms in. diabetic rat glomerular cells. Diabetes 1998:47:668-676
[16]Weiss RH, Ramirez A. TGF-beta-and angiotensin-ll-induced mesangial matrix protein secretion is mediated by protein kinase C. Nephrol Dial Transplant 1998:13:2804-2813
[17]Tuttle KR,Anderson PW.A novel potential therapy for diabeticnephropathy and vascular complications:ProteinKinase C β inhibition.Am J Kid Dis.2003;42 (3):456-465
[18]倪青.糖尿病肾病的中医药研究思路与方法[J].中国医药学报,1998,13(4)：60-62
[19]吕仁和.糖尿病及其并发症中西医诊治学[M].北京：人民卫生出版社,2001,328
[20]林兰.中西医结合糖尿病学．北京：中国医药科技出版社,1999：394[20]曲晓璐,陈大舜,姚欣艳,等.1718例2型糖尿病患者糖尿病肾病发病率及其中医证型分布特点.中国中西医结合肾病杂志,2003,4(12)：713
[21]倪青.活血化瘀法治疗糖尿病肾病42例.南京中医药大学学报,2003,19(6)：380
[22]张琪,吴长富,缪胜尧.消渴益肾汤治疗糖尿病肾病的疗效观察.河北中医,1994,(5)：8
[21]成玉斌,罗仁，胡志飞,等.糖尿病肾病中医辨证分型荟萃分析.中国中医基础医学杂志,2000,6(5)：49
[22]杨霓芝,王立新,廖平平.248例糖尿病肾病患者分期辨证分析.广州中医药大学学报,1998,15(4)：260
[23]李毅.祝堪予老中医活血化瘀法治疗糖尿病经验[J].山东中医学院学报.1986,9(5)：27
[24]陈辉,汤水福,赵萍.活血化瘀法治疗早期糖尿病肾病及其对肾血流参数的影响[J].中国中西医结合肾病杂志.2005,6(1)：31
[25]郭赛珊.治疗糖尿病肾病的经验体会．中国中西医结合杂志,1996,16(1)：3
[26]吕仁和,时振声.糖尿病肾病的中医诊治[J].北京中医,1989,8(2)：8-10.
[27]林兰.中西医结合糖尿病学.北京：中国医药科技出版社,1999：394
[28]熊曼琪,苗理平.加味桃核承气汤对糖尿病鼠肾超微结构的影响[J].中国医药学报,1990,5(5)：25-27.
[29]张泽生,袁遵守,杨新军,等.益肾扶脾化瘀降浊法治疗糖尿病肾病64例临床观察.新中医,2001,33(11)：36
[30]林兰.糖尿病中西医结合论治[M].北京：北京科学技术出版社1992,229.
[31]高彦彬,易京红.糖肾宁治疗糖尿病肾病的临床研究.中医杂志,1991,32(7)：31
[32]陈辉,汤水福,赵萍.活血化瘀法治疗早期糖尿病肾病及其对肾血流参数的影响[J].中国中西医结合肾病杂志.2005,6(1)：31
[33]郭赛珊.治疗糖尿病肾病的经验体会.中国中西医结合杂志,1996,16(1)：3
[34]吕仁和,时振声.糖尿病肾病的中医诊治[J].北京中医,1989,8(2)：8-10.
[35]张泽生,袁遵守,杨新军,等.益肾扶脾化瘀降浊法治疗糖尿病肾病64例临床观察.新中医,2001,33(11)：36
[36]林兰,倪青,董彦敏.糖尿病肾病中西医结合治疗热点问题述评[J]．中西医结合杂志,2000,7：50
[37]高彦彬,易京红.中医药辩治糖尿病肾病100例临床分析[J].中医杂志,1991,32(7)：31-32
[38]邓权.益肾活血法治疗糖尿病肾病62例[J].浙江中医杂志,1996,31(7)：317-318
[35]耿嘉,栗德林.糖尿病肾病病因病机的辩证.首都医药,2005,3：(12)：112
[36]吉勤,王清,李桢,等.活血化瘀法改善糖尿病肾病水肿的疗效观察[J].中国中西医结合肾病杂志,2006,7(2)：109
[37]孙树良,郑杨.活血化瘀法治疗糖尿病肾病临床观察[J].辽宁中医学院学报,2006,8(2)：84-85
[38]睦书魁,李细贵.从瘀论治糖尿病57例临床观察[J].中国中西医结合杂志,1992,12(1)：43.11
[39]耿嘉,栗德林.糖尿病肾病病因病机的辩证.首都医药,2005,3：(12)：112
[40]刘冰冰.糖尿病神经病变患者血液流变性与微循环指标分析.中国血液流变学杂志.2000,10(1)：47-49
[40]张宗铭.糖尿病瘀血产生的机理、辨证与治疗[J]安徽中医学院学报,1989,(2)：53-56
[41]石志芸,等.血栓相关分子标志物在糖尿病血瘀证中的临床意义[J]中医杂志,1999,40(9)：554-555
[42]曾庆祥.糖尿病肾病从瘀论治[J].吉林中医药,2001,21(3)：14
[43]林兰,倪青,董彦敏.糖尿病肾病中西医结合治疗热点问题述评[J].中西医结合,2000,7：50.
[41]翁维良.糖尿病人”瘀血”的研究[J]中医杂志,1982,1(1)：46-48
[42]吴春林.试析糖尿病从瘀论治的理论基础[J]．长春中医学院学报1997,13(4)：3
[43]刘冰冰.糖尿病神经病变患者血液流变性与微循环指标分析.中国血液流变学杂志.2000,10(1)：47-49
[44]石志芸,等.血栓相关分子标志物在糖尿病血瘀证中的临床意义(J)中医杂志,1999,40(9)：554-555
[45]施赛珠,王倩,董彩云.Ⅱ型糖尿病中瘀血证和益气活血药预防其血管病变的疗效观察.中医杂志,1989,30(6)：341
[46]方立成.化瘀养阴汤治疗Ⅱ型糖尿病56例临床观察.湖南中医学院学报,1994,14(2)：20
[47]赵淑华,严庆良.糖尿病患者平均血小板体积和高脂变化的研究．中华内分泌代谢杂志,1998,14(1)：42
[48]梁晓春,王秀定,张孟仁.糖尿病患者血浆TXB2.6-K-PGFla水平、全血粘度与血瘀证的微血管病的关系.中国中西医结合杂志,1992,12(5)：29[47]刘新明,刘晓城.糖尿病肾病的发病机制与治疗现状.中国中西医结合肾病杂志,2004,5(9)：553-554
[49]NavarroJF,MoraC,MacaM,et al. Inflammationtory parameters are independently associated with urinary albumin in type 2 diabetes mellitus. Am J Kidney Dis,2003,42:53-61.
[50]Anders H J, Vielhauer V, Schlondorff D. Chemokines and chemokine receptors are involved in the resolution or progression of renal disease.Kidney Int,2003,63:401-415.
[51]Mensah-Brown EPK, Obineche EN, Galadari S,et al. Streptozotocin-induced diabetic nephropathy in rats:The role of inflammatory cytokines. CYTOKI NE,2005,31 (3):180-190.
[52]Lee SH, Lee TW, Ihm CG, et al. Genetics of diabetic nephropathy in type 2 DM:candidate gene analysis for the pathogenic role ofinflammation. Nephrology,2005,10:S32-S36.
[53]Navarro JF,Mora C. Role of inflammation in diabetic complications. Nephrology dialysis transplantation,2005,20(12):2601-2604.
[54]Sfakianaki M, Xydakis D, Papadogiannakia A,et al.l Low-grade inflammation is correlated to diabetic nephropathy in type 2 diabetes mellitus. Diabetologia,2005,48:A375-A376.
[55]Lee SH, Lee TW, Ihm CG, et al. Genetics of diabetic nephropathy in type 2 DM:candidate gene analysis for the pathogenic role ofinflammation. Nephrology,2005,10:S32-S36.
[56]王海松,谢春光.益肾糖泰颗粒对糖尿病大鼠肾脏病变的影响[N].成都中医药大学学报,2000,23(1)：49-57
[57]李建生,郑士荣.中药糖肾安对实验性糖尿病大鼠肾脏病变的作用[J]河南中医,1995,15(5)：282284
[58]武慧,杜宏武,谢道俊,等.益气养阴活血化淤法为主治疗老年早期糖尿病肾病31例[N].安徽中医学院学报,2001,20(1)：16-8
[59]姜春华.活血化瘀研究[M].上海：上海科技出版社,1981,1：341.
[60]Navarro JF,Mora C. Role of inflammation in diabetic complications. Nephrology dialysis transplantation,2005,20(12):2601-2604.
[61]Sfakianaki M, Xydakis D, Papadogiannakia A,et al.l Low-grade inflammation is correlated to diabetic nephropathy in type 2 diabetes mellitus. Diabetologia,2005,48:A375-A376.
[62]Idris I, Gray S,Donnelly R. Protein kinase C activation: isozymespecific effects on metabolism and cardiovascular comp lications in diabetes. Dia2betologia,2001,4:6592673.
[63]Nishizuka Y.Intracellar signaling by hydrolysis of phospholipids and activation of protein kinase C. Science,1992,258:607
[64]Williams B, Schrier RW.Glucose-induced protein kinase C activitityregulates arachidonic acid release and eicosanoid . production by cultured glomerular mesangial cells.) Clin Invest, 1993,92:2889
[65]Sharma K, Jin Y, Guo J. Neutralization of TGF-} antibody attenuates kidney hypertrophy and the enhanced extracellular matrix. geneexpression in STZ-induced diabete mice. diabetes,1996,45:522
[66]Messina JL, Standaert ML. Ishizuka T. Role of protein kinase C in insulin's regulation of c-fos transcription. J Biol Chem,1992, 267:9223
[67]Sharma K, Danoff V, Depiero A. Enhanced expression of inducible nitric oxide synthase in murine macrophages and glomerular
mesangial cells by elevated glucose levels:possible mediation via protein kinase C.Biochem Biophys Res Commun,1995,207:80
[68]Craven PA, Studer RK, Derubertis FR. Impaired nitric oxide-dependentcGMP generation in glomeruli from diabetic rats. J Clin Invest,1994,93:311
[69]Fukui M, Nakamura T, Ebihara Ⅰ. ECM gene expression and its modulation by insulin in diabetic rat s. Diabetes,1992,41:1520
[70]Sharma K, Jin Y, Guo J. Neutralization of TGF-} antibody attenuates kidney hypertrophy and the enhanced extracellular matrix gene expression in STZ-induced diabete mice. diabetes,1996,45:522
[71]Messina JL, Standaert ML. Ishizuka T. Role of protein kinase C in insulin's regulation of c-fos transcription. J Biol Chem,1992, 267:9223
[72]Xia P, Kramer RM, King GL. Identification of the mechanism for the inhibition of Na, K-ATPase by hyperglycemia involving activation of protein kinase C and cytolic phospholipase A2.J Clin Invest,1995 96:733
[73]KellyDJ, Zhang Y, HepperC, et al. Kinase C beta inhibition. Am J Kidney Dis,2003,42:456-465.
[74]Ahmad FK, He Z, King GL. Moleculartargets of diabetic cardiovascular complications. Curr Drug Targets,2005,6:487— 494.
[75]W illiams M E, Tuttle KR The next generation of diabetic nephropathy therapies:an update. Adv Chronic Kidney Dis, 2005,12:212-222.
[76]Ha H,Yu MR,Choi YJ,et al.Activation of protein kinase C-delta and C-epsilon by oxidative stress in early diabetic rat kidney.Am J Kidney Dis,2001,384:$204-S207.
[77]Wolf G,Ziyadeh,FN,Stahl RA.Angiotensin II stimulates expression of transforming growth factor beta receptor type II in cultured mouse proximal tubular cells[J].JMohned,1999,77 (5):556-564
[78]Rollins BJ, Walz A, Baggiolini M. Recombinant human MCP-1/JE induces chemotaxis, calcium flux, and the respiratory burst in human monocytes.Blood.1991 Aug 15;78(4):1112-6.
[79]Wada T, Furuichi K, Sakai N, Iwatay etal. Up-regulation of monocytechemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy.Kidney Int.2000 Oct;58(4):1492-9.
[80].Mezzano SA, Droguett MA, Burgos ME, etal. Overexpression ofchemolkines, fibrogenic cytol}ines, and myofibroblasts in human membranous nephropathy.Kidney Int. 2000 Jan;57(1):147-58.
[81]Wada T, Furuichi K, Sakai N, Iwata Y, etal. Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy.Kidney Int.2000 Oct;58(4):1492-9.
[82]Mezzano SA, Droguett MA, Burgos ME, etal. Overexpression of chemolkines, fibrogenic cytolkines, and my ofibro blastsin human membranous nephropathy.Kidney Int.2000 Jan;57(1):147-58.
[83]Cooper ME.Pathogenesis, prevention, and treatment of diabetic nephropathy.Lancet.1998 Jul 18:352(9123):213-9.
[84]顾勇,赖凌云.肾素一血管紧张素系统在糖尿病肾病研究中的进展.中华肾脏病杂志,2004,3：22
[85]Van Kat JP,De Lannoy LM.Jan Danser AH,et al.Angiotensin type
1 (AT1)receptor mediated accumulation of angiotensin in tissues and its intracellular half-life in vivo.Hypertension,1997,30:42-49.
[86]Banba N, Nakamura T, Matsumura M, Kuroda H, Hattori 丫 Kasai K. Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropdthy.Kidney Int.2000 Aug;58(2):684-90.
[87].Ruiz-Ortega M, Lorenzo O, Egido J. Angiotensin III increases MCP-1 and activates NF-kappaB and AP-1 in cultured mesangial and mononuclear cells.Kidney Int.2000 Jun;57(6):2285-98.
[88].文晖,林善欢.血管紧张素受体拮杭剂颧沙坦对糖尿病大鼠肾脏的保护作用.中华内科杂志,1999,3：160.
[89].Branton MN,Kopp JB.TGF-beta and ftbrosis.Microbes Infect, 1998;1(15):1349-1365
[90]lxe HB, HaH.Plasminogen activator inhibitor-1 and diabetic nephropathy.Nephrology (Carlton).2005 Oct;10 Suppl:S11-3.
[91]KorpinenE, Teppo AM, Hukkanen L, et al. Urinary transforming growth factorpl and al-microglobulin in children and adolescents with type 1 diabetes.Diabetes
[92]Hill C, Logan A, Smith C, et al. Angiotensin conveting enzyme inhibi suppresses glomerular transforming growth factor beta receptor expression experimental diabetes in rats. Diabetologia,2001;44(4):496-500
[93]EllisD} Forest K}} Erbey J} Orchard TJ. Urinary measurement of transformer growth factor-beta and type N collagen as new markers of repinjury:application in diabetic nephropathy. Clin Chem,1998;44(5):950-956
[94]荆春艳,叶山东,陈燕等糖尿病患者尿转化生长因子131检测的临床意义安徽医科大学学报,2003；38(3)：202-204
[95]ShanlandSJ} Scholey Jw. Expression of transforming growth factorBI during diabetic renal hypertrophy.Kidney Int,1994:46:430-436
[96]Bertoluci MC. Transforming growth factor B in the development of rat diabetic nephropathy. A 10-month study with insulin-treated rats. Nephron,1996; 10(9):1891-1899
[97]Yagi K, Kim S, Wanibuchi H. Characteristics of diabetes, blood pressure, and cardiac and renal complications in Otsuka Long-Evans Tokushima Fattyrats [J]. Hypertension,1997,29 (3):728-735
[98]Schafer S, Linz W, Bube A, et al. Vasopeptidase inhibition prevents nephropa -thy in Zucker diabetic fatty rats [J].CardiovascRes,2003,60(2):447-454
[99]Yagi K, Kim S, Wanibuchi H. Characteristics of diabetes, blood pressure, and cardiac and renal complications in Otsuka Long-Evans Tokushima Fattyrats [J]. Hypertension,1997,29 (3):728-735
[100]Pavan MV, Ghin B, Castro M, et al. Prevention of hypertension atten-uates albuminuria and renal expression of fibronectin in diabetic spont-aneously hypertensive rats [J]. AmJNephrol,2003,23(6):422-428
[101]Gross ML, Ritz E, Schoof A, et al. Comparison of renal morphology in the streptozotocin and the SHR/N-cp models of diabetes [J].Lablnvest,2004,84:452-464
[102]Raz I, Wexler I, Weiss O, et al. Role of insulin and the IGF system in renal hypertrophy in diabetic Psammomys obesus (sand rat) [J].Nephrol Dial Transplant,2003,18(7):1293-1298
[103]Cusumano AM, Bodkin NL, Hansen BC, et al. Glomerular hyper-trophy is associated with hyperinsulinemia and precedes overt
diabetes in aging rhesus monkeys [J]. Am J Kidney Dis,2002,40 (5):1075-1085
[104]Kelly DJ, Wilkinson-Berka JL, Allen TJ, et al. A new model of diabetic nephropathy with progressive renal impairment in the transg-enic (mRen-2)27 rat (TGR)[J]. Kidney Int,1998,54:343-352
[105]Wogensen L, Nielsen CB, Hjorth P, et al. Under control of the renal promoter, locally produced transforming growth factor-betal induces accumulation of glomerular extracellular matrix in transgenic mice [J]. Diabetes,1999,48(1):182-192
[106]Yamamoto Y, Kato I, Doi T, et al. Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice [J]. JClin Invest,2001,108:261-268
[107]北京制药工业研究所.川芎嗪有效成分的研究-川芎嗪的提取、分离和结构鉴定[J].中华医学杂志,1977,57(7)：420.
[108]北京制药工业研究所.川芎嗪有效成分的研究-川芎嗪的药理研究[J].中华医学杂志,1977,57：464.
[109]曾健英,罗正茂,张建林.川芎嗪治疗糖尿病肾病68例.广东医学,2005,26(7)：1004-1005
[110]赵秀珍,川芎嗪针剂对早期糖尿病肾病疗效观察.医药论坛杂志,2004,25(6)：31-33
[111]崔哲,陈馥,谷素洁,等.川芎嗪对老年糖尿病肾病病人肾功能及血脂的影响.人民军医,2006,49(4)：190-191
[112]赵秀珍.川芎嗪针剂对早期糖尿病肾病疗效观察[J].医药论坛,2004；25(6)：31-32
[113]阮颖新,李丽英,陈云波,等.1型糖尿病与2型糖尿病血脂变化比较[J].哈尔滨医科大学学报,2004；38(1)：94-95
[114]杨巧芝,吕学云,于爱菊.川芎嗪对肾病综合征血脂及载脂蛋白的变化的临床研究[J].中国当代儿科杂志,2002；4(6)：491-492
[115]王玉良.川芎嗪对心血管组织的药理和电生理作用-一种新的钙拮抗剂[J]．中西医结合杂志,1985,5(5)：291.
[116]Bianchis, Bigazzi R, Canpese V. Micralbuminuria in essential hypertension [J]. Am J Kidney Dis,1999:34:973
[117]王力宁,糖尿病肾病的非血液净化治疗[J].肾脏病与透析肾移植杂志,2003,12(5)：443
[118]梁锋,赵敏毅.洛汀新和葛根素治疗糖尿病肾病的临床疗效[J].实用医技杂志,2006,13(4)：544
[119]陈淑娇,郑京.ACEl、ARB阻止糖尿病肾病发展的机制[J].现代实用医学,2004,16(12)：741
[120]熊燕,贾汝汉.肾素-血管紧张素系统在糖尿病肾病发病机制中的新认识.中国中西医结合肾病杂志,2004,5(9)：553～555
[121]Li C, Yana CW.Park CW.et al. Long-term trealment w ith ramipril auenuales renal osleoponlin expression in diahelic rats. Kidney Inl, 2003,63(2):454-463
[122]邢淑丽,郑君芙,黄文政.单侧肾切除STZ诱导糖尿病肾病大鼠动物模型研究.中国中医急症杂志,2006；(15)6：643-644
[123]顾明,邵凤民.肾小管间质纤维化机制的研究进展.医药论坛杂志,2005,26：(5)70-73
[124]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)：811-814
[125]冯建春,倪青.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)：212-214
[126]宫伟星,姜新国,王俊基,等.糖肾通宝饮治疗早期糖尿病肾病的临床研究[J].山东中医药大学学报,2000,24(2)：111-113
[127]于淼.糖尿病肾病中药复方实验研究进展[J].长春中医学院学报,2004,20(1)：57-59
[128]谢席胜.糖尿病肾病单味中药研究进展[J].中医药研究,2002,18(6)：47-48
[129]邵倩,陈福琴.川芎嗪在糖尿病肾病中的应用及其机制研究.中国中西医结合肾病杂志,2002,3(12)：739-741
[130]于淼.糖尿病肾病中药复方实验研究进展[J].长春中医学院学报,2004,20(1)：57-59
[131]翁孝刚,郭永年,王道刚,等.川芎嗪治疗糖尿病慢性并发症.新乡医学院学报；1993,10(3)：187.
[132]唐诗伟,朱红倩,晏永慧,等.川芎嗪治疗2型糖尿病肾病38例观察.实用中医药杂志,1999,15(8)：3-4
[133]顾碧云,戴晓星,张允亭,等.川芎嗪对糖尿病血液高凝状态的影响[J].中西医结合杂志,1989,9(5)：320
[134]吴建平,沈世忠,杨忠民.川芎嗪对肾病综合征肾功能、血脂及血液流变学的影响[J].中华肾脏病杂志,1999,15(3)：169
[135]熊旭明,梁剑波,潘巧红,等.尿视黄醇结合蛋白与糖尿病肾病.中华肾脏病杂志.1997,13(4)：215
[136]杨沛,陈伟,姚春燕.糖尿病肾病的早期诊断.中国现代医学杂志.2002,3(5)：48-50
[137]陈海英，沈稚舟.2型糖尿病病人微量白蛋白的影响因素.中国实验诊断杂志.1998,2(1)：18-21
[138]LiC,Yang Park renalosteopont in expression etal.Long-term treatment with ramipril attenuates in diabetic rats. Kidney Int,2003, 63:454-463
[139]Abdel-Wahab N, Yevdokimova N,Weston BS etal. Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy. BiochemJ,2001;359(1):77-87
[140]张卫平.浅谈活血化瘀法在糖尿病肾病治疗中的运用.实用中医药杂志,2003,19(5)；268
[141]Wada T,Furuichi K,Sakai N, et al.Gene therapy via blockade of monocyte chemoattractant protein-1 for renal fibrosis. J Am Soc Nephrol,2004,15:940-948.
[142]Panzer U,Thaiss F,Zahner G,et al. Monocyte chemoattractant protein-1 and osteopontin differentially regulate monocytes recruitment in experimential glomerulonephritis.Kidney Int,2001,59 (5):1762-1769.
[143]于世鹏,郭焕,王雪等.楠糖尿病肾病患者MCP-1和OPN变化及意义[J].山东医药,2007,47(28)：46-47.
[144]刘国元.TGF-β1与肾小球硬化关系的研究[J]国外医学泌尿系统分册,2002,22(6)：361-363
[145]Li JH, Zhu HJ, Huang XR, et al. Smad 7 inhibits fibrotic effect of TGF-beta on renal tubular epithelial cells by blocking smad2 activation [J].J Am Soc Nephrol,2002,13:1464-1472.
[146]Koya D, King Gl.. Protein kinase C activation and the development of diabetic complications. Diabetes.1998:47:859-866
[147]Haneda M, Koya D, Kikkawa R. Cellular mechanisms in the development and progression of diabetic nephropathy:activation of the DAG-PKC-ERK pathway. Am J Kidney Dis.2001:38(4 Suppl 1):S178-81
[148]Ways DK, Sheetz MJ. The role of protein kinase C in the development of the complications of diabetes. Vitam Horm.2000;60:149-93
[149]Whiteside Cl, Dlugosz JA. Mesangial cell protein kinase C isozyme activation in the diabetic milieu. Am J Physiol Renal Physiol 2002 Jun;282 (6):F975-80
[150]吴永贵,林善琐.蛋白激酶C与糖尿病肾病.中华肾脏病杂1998；14(6)399-402
[151]RaptisAE, VibertiG.Pathogenesis of diabetic nephropathy. ExpClin Endocrinol Diabeties 2001:109 (suppl2):5424-437
[152]Ganz M, Saxena R, Hawkins K, et al. PDGF and IL-1 induce and activate specific protein C isoforms in mesangial cells. Am J Physiol Renal Fluid Electrolyte Physiol 1996:271:F108-F113
[153]Pfaff IL, Vallon V. Protein kinase C beta isoenzymes in diabetic kidneys and their relation to Nephroprotective actions of the ACE inhibitor Lisinopril. Kidney Blood Presss Res 2002:25:329-340
[1]Anderson AR, et al. Diabetic nephropathy in type 1 (insulin-dependent) diabetes:An epidemiological study. Diabetologia, 1983,23 B496
[2]孙建红,何戎华,任传路.虫草制剂和开博通对糖尿病大鼠肾脏功能和形态影响的对比研究.徐州医学院学报,2000,20(6)：450-453
[3]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.现代中医药,2007,27(3)：69-71
[4]艾智华,蔡红卫,张忠辉.大黄酸治疗大鼠糖尿病肾病的实验研究.第三军医大学学报,2004,26(4)：304-306
[5]柴可夫,柴瑞.糖肾汤对糖尿病大鼠肾脏保护作用的实验研究.中医药学刊,2005,23(9)：1551-1552
[6]李佑生,王文健,马宇滢,等.复方丹参滴丸防治大鼠早期糖尿病肾脏损害的研究.中成药,2007,(1)：40-44
[7]张莹雯,谢丹,杜光,等.归芪方合苯那普利对糖尿病大鼠肾组织转化生长因子β1的影响.中国中西医结合杂志,2005年6月第25卷基础理论研究特集86～90
[8]朱国茹,石岩,马丽佳.糖肾保煎剂和雷米普利对糖尿病大鼠肾脏保护作用的对比实验.中国中医药信息杂志,2005,12(1)：30-32
[9]苏小惠.中西医结合治疗糖尿病肾病40例临床观察.辽宁中医杂志.2006,33(1)：92-93
[10]王国芝,张莉,屈云.糖尿病肾病的中西医结合治疗的临床研究[]].现代中医药,2003,(4)：36-38
[11]张焱.中西医结合治疗糖尿病肾病30例的临床观察.生临床和实验医学杂志.2006,5(4)：402-403
[12]陈望善,杨玉霞,李华.中西医结合治疗糖尿病肾病的临床观察.湖北中医杂志.2004,26(12)：9-10
[13]胡宝峰,李秋英,任小强,等.补阳还五汤加味治疗早期糖尿病肾病56例.陕西中医,2005,26(12)：1281-1282
[13]林楠,宋王宣,薛丽.通心络胶囊治疗糖尿病肾病疗效观察.中国误诊学杂志.2005,5(9)：1663-1664
[14]宋晓燕,陈蔷,齐晓燕.六味地黄丸对早期糖尿病肾病患者红细胞醛糖还原酶活性的影响.中国中西医结合杂志.2004,24(12)：1087-1090
[15]陈弼沧,吴秋英.血府逐瘀口服液治疗糖尿病肾病的临床观察.吉林中医药.2003,23(1)：15-16
[17]尹红梅.川芎嗪与山莨菪碱治疗糖尿病肾病40例.临床荟萃.2000,15(12)：553-554
[18]黄各宁,陈积优,张镁元.灯盏花素注射液对糖尿病肾病血液流变学影响的临床研究.新.2006,38(3)：34-35
[19]杨益芳.葛根素注射液治疗50例糖尿病肾病的疗效观察.泸州医学院学报.2003,26(1)：44-45
[20]曹骥翔,唐新玉,丁亮,等.黄芪、生脉注射液联合苯那普利治疗糖尿病肾病32例疗效观察.湖南中医药导报.2002,8(10)：596-597
[21]杨燕,邸阜生,李坤.静黄芪丹参注射液与开博通联合应用治疗糖尿病肾病.临床观察天津医科大学学报.2000,6(1)：79-81
[22]史伟,唐爱华,吴金玉,等.水蛭注射液治疗糖尿病肾病57例疗效观察.新中医.2006,38(3)：38-40
[23]马为,唐桂军,郭泉滢.杏丁注射液治疗糖尿病肾病52例.中医研究.2004,17(2)：31-32
[24]刘香春.中药灌肠法治疗糖尿病肾病肾功能不全30例.四川中医．2006,24(4)：68-69
[25]王秀霞,李富英.中药灌肠合灸神厥穴对糖尿病晚期肾病的影响.山东医药.2006,46(28)：72
[2]Li Ls.End-stage renal disease in China. [J]. Kidney Int,1996,49:287.
[3]Raij L. Recommendation for the management of special populations: renal disease in diabetes. Am J Hypertens,2003,16:46-49
[4]佟之复,李宁华,苗俊梅等.2型糖尿病肾病流行病学研究进展[J].中国老年学杂志,2001,21(3)：241-243.
[5]Brownlee M, Cerami Vlassara H, et al. Advanced glycosylation end products
in tissue and the biochemical basis of diabetic complications. N Engl J Med,1988,318:1315
[6]刘志红,黎磊石.榕尿病肾病发病机理.中华肾脏病杂志,1999,15(2)：121
[7]朱禧星.现代搪尿病学.第1版上海：上海医科大学出版社,2000；319
[8]吴永贵,林辉,钱浩,等.灯盏花素对大鼠糖尿病模型肾组织TGFβ1与CTGF表达影响的实验研究.中国药理学通报,2004；20(9)：1050-4
[9]Phillip sAO, Steadman R, Diabetic nephropathy:the central role of renal proximal tubular cells in tubulointerstitial injury. Histol Histopathol, 2002,17(1):247-252
[10]苏宁,罗容敬,邝枣园,等TGF—β1对糖尿病肾病早期ECM沉积影响的实验研究[J].中国实用医药,2007,11(2)：57-59
[11]Haneda M, Koya D, Kikkawa R. Cellular mechanisms in the development and progression of diabetic nephropathy:activation of the DAG-PKC-ERK pathway. Am J Kidney Dis.2001:38(4 Suppl 1):S178-81
[12]Ways DK, Sheetz MJ. The role of proteinof the complications of diabetes. Vitamkinase C in the developmentHorm.2000:60:149-93
[13]Koya D, Kikkawa R, Kashiwagi A, et al. Activation of Protein Kinase C-Mitogen Activated Protein Kinase Pathway and Diabetic Nephropathy. CIN'2003'3th congress of nephropathy in Internet. http://www.unmet.edu/cin2003/conf/koya/koya html
[14]Sheetz MJ,King GL.Molecular under-standing of hyperglycemia's adverse effects for diabetic complications. JAMA.2002:288:2579-88.
[15]Babazono T, Kapor-Drezgic J, Dlugosz JA, et al. Altered expression andsubcellular localization of diacylglycerol-sensitive protein kinase C isoforms in. diabetic rat glomerular cells. Diabetes 1998:47:668-676
[16]Weiss RH, Ramirez A. TGF-beta-and angiotensin-ll-induced mesangial matrix protein secretion is mediated by protein kinase C. Nephrol Dial Transplant 1998:13:2804-2813
[17]Tuttle KR,Anderson PW.A novel potential therapy for diabeticnephropathy and vascular complications:ProteinKinase C β inhibition.Am J Kid Dis.2003;42 (3):456-465
[18]倪青.糖尿病肾病的中医药研究思路与方法[J].中国医药学报,1998,13(4)：60-62
[19]吕仁和.糖尿病及其并发症中西医诊治学[M].北京：人民卫生出版社,2001,328
[20]林兰.中西医结合糖尿病学．北京：中国医药科技出版社,1999：394[20]曲晓璐,陈大舜,姚欣艳,等.1718例2型糖尿病患者糖尿病肾病发病率及其中医证型分布特点.中国中西医结合肾病杂志,2003,4(12)：713
[21]倪青.活血化瘀法治疗糖尿病肾病42例.南京中医药大学学报,2003,19(6)：380
[22]张琪,吴长富,缪胜尧.消渴益肾汤治疗糖尿病肾病的疗效观察.河北中医,1994,(5)：8
[21]成玉斌,罗仁，胡志飞,等.糖尿病肾病中医辨证分型荟萃分析.中国中医基础医学杂志,2000,6(5)：49
[22]杨霓芝,王立新,廖平平.248例糖尿病肾病患者分期辨证分析.广州中医药大学学报,1998,15(4)：260
[23]李毅.祝堪予老中医活血化瘀法治疗糖尿病经验[J].山东中医学院学报.1986,9(5)：27
[24]陈辉,汤水福,赵萍.活血化瘀法治疗早期糖尿病肾病及其对肾血流参数的影响[J].中国中西医结合肾病杂志.2005,6(1)：31
[25]郭赛珊.治疗糖尿病肾病的经验体会．中国中西医结合杂志,1996,16(1)：3
[26]吕仁和,时振声.糖尿病肾病的中医诊治[J].北京中医,1989,8(2)：8-10.
[27]林兰.中西医结合糖尿病学.北京：中国医药科技出版社,1999：394
[28]熊曼琪,苗理平.加味桃核承气汤对糖尿病鼠肾超微结构的影响[J].中国医药学报,1990,5(5)：25-27.
[29]张泽生,袁遵守,杨新军,等.益肾扶脾化瘀降浊法治疗糖尿病肾病64例临床观察.新中医,2001,33(11)：36
[30]林兰.糖尿病中西医结合论治[M].北京：北京科学技术出版社1992,229.
[31]高彦彬,易京红.糖肾宁治疗糖尿病肾病的临床研究.中医杂志,1991,32(7)：31
[32]陈辉,汤水福,赵萍.活血化瘀法治疗早期糖尿病肾病及其对肾血流参数的影响[J].中国中西医结合肾病杂志.2005,6(1)：31
[33]郭赛珊.治疗糖尿病肾病的经验体会.中国中西医结合杂志,1996,16(1)：3
[34]吕仁和,时振声.糖尿病肾病的中医诊治[J].北京中医,1989,8(2)：8-10.
[35]张泽生,袁遵守,杨新军,等.益肾扶脾化瘀降浊法治疗糖尿病肾病64例临床观察.新中医,2001,33(11)：36
[36]林兰,倪青,董彦敏.糖尿病肾病中西医结合治疗热点问题述评[J]．中西医结合杂志,2000,7：50
[37]高彦彬,易京红.中医药辩治糖尿病肾病100例临床分析[J].中医杂志,1991,32(7)：31-32
[38]邓权.益肾活血法治疗糖尿病肾病62例[J].浙江中医杂志,1996,31(7)：317-318
[35]耿嘉,栗德林.糖尿病肾病病因病机的辩证.首都医药,2005,3：(12)：112
[36]吉勤,王清,李桢,等.活血化瘀法改善糖尿病肾病水肿的疗效观察[J].中国中西医结合肾病杂志,2006,7(2)：109
[37]孙树良,郑杨.活血化瘀法治疗糖尿病肾病临床观察[J].辽宁中医学院学报,2006,8(2)：84-85
[38]睦书魁,李细贵.从瘀论治糖尿病57例临床观察[J].中国中西医结合杂志,1992,12(1)：43.11
[39]耿嘉,栗德林.糖尿病肾病病因病机的辩证.首都医药,2005,3：(12)：112
[40]刘冰冰.糖尿病神经病变患者血液流变性与微循环指标分析.中国血液流变学杂志.2000,10(1)：47-49
[40]张宗铭.糖尿病瘀血产生的机理、辨证与治疗[J]安徽中医学院学报,1989,(2)：53-56
[41]石志芸,等.血栓相关分子标志物在糖尿病血瘀证中的临床意义[J]中医杂志,1999,40(9)：554-555
[42]曾庆祥.糖尿病肾病从瘀论治[J].吉林中医药,2001,21(3)：14
[43]林兰,倪青,董彦敏.糖尿病肾病中西医结合治疗热点问题述评[J].中西医结合,2000,7：50.
[41]翁维良.糖尿病人”瘀血”的研究[J]中医杂志,1982,1(1)：46-48
[42]吴春林.试析糖尿病从瘀论治的理论基础[J]．长春中医学院学报1997,13(4)：3
[43]刘冰冰.糖尿病神经病变患者血液流变性与微循环指标分析.中国血液流变学杂志.2000,10(1)：47-49
[44]石志芸,等.血栓相关分子标志物在糖尿病血瘀证中的临床意义(J)中医杂志,1999,40(9)：554-555
[45]施赛珠,王倩,董彩云.Ⅱ型糖尿病中瘀血证和益气活血药预防其血管病变的疗效观察.中医杂志,1989,30(6)：341
[46]方立成.化瘀养阴汤治疗Ⅱ型糖尿病56例临床观察.湖南中医学院学报,1994,14(2)：20
[47]赵淑华,严庆良.糖尿病患者平均血小板体积和高脂变化的研究．中华内分泌代谢杂志,1998,14(1)：42
[48]梁晓春,王秀定,张孟仁.糖尿病患者血浆TXB2.6-K-PGFla水平、全血粘度与血瘀证的微血管病的关系.中国中西医结合杂志,1992,12(5)：29[47]刘新明,刘晓城.糖尿病肾病的发病机制与治疗现状.中国中西医结合肾病杂志,2004,5(9)：553-554
[49]NavarroJF,MoraC,MacaM,et al. Inflammationtory parameters are independently associated with urinary albumin in type 2 diabetes mellitus. Am J Kidney Dis,2003,42:53-61.
[50]Anders H J, Vielhauer V, Schlondorff D. Chemokines and chemokine receptors are involved in the resolution or progression of renal disease.Kidney Int,2003,63:401-415.
[51]Mensah-Brown EPK, Obineche EN, Galadari S,et al. Streptozotocin-induced diabetic nephropathy in rats:The role of inflammatory cytokines. CYTOKI NE,2005,31 (3):180-190.
[52]Lee SH, Lee TW, Ihm CG, et al. Genetics of diabetic nephropathy in type 2 DM:candidate gene analysis for the pathogenic role ofinflammation. Nephrology,2005,10:S32-S36.
[53]Navarro JF,Mora C. Role of inflammation in diabetic complications. Nephrology dialysis transplantation,2005,20(12):2601-2604.
[54]Sfakianaki M, Xydakis D, Papadogiannakia A,et al.l Low-grade inflammation is correlated to diabetic nephropathy in type 2 diabetes mellitus. Diabetologia,2005,48:A375-A376.
[55]Lee SH, Lee TW, Ihm CG, et al. Genetics of diabetic nephropathy in type 2 DM:candidate gene analysis for the pathogenic role ofinflammation. Nephrology,2005,10:S32-S36.
[56]王海松,谢春光.益肾糖泰颗粒对糖尿病大鼠肾脏病变的影响[N].成都中医药大学学报,2000,23(1)：49-57
[57]李建生,郑士荣.中药糖肾安对实验性糖尿病大鼠肾脏病变的作用[J]河南中医,1995,15(5)：282284
[58]武慧,杜宏武,谢道俊,等.益气养阴活血化淤法为主治疗老年早期糖尿病肾病31例[N].安徽中医学院学报,2001,20(1)：16-8
[59]姜春华.活血化瘀研究[M].上海：上海科技出版社,1981,1：341.
[60]Navarro JF,Mora C. Role of inflammation in diabetic complications. Nephrology dialysis transplantation,2005,20(12):2601-2604.
[61]Sfakianaki M, Xydakis D, Papadogiannakia A,et al.l Low-grade inflammation is correlated to diabetic nephropathy in type 2 diabetes mellitus. Diabetologia,2005,48:A375-A376.
[62]Idris I, Gray S,Donnelly R. Protein kinase C activation: isozymespecific effects on metabolism and cardiovascular comp lications in diabetes. Dia2betologia,2001,4:6592673.
[63]Nishizuka Y.Intracellar signaling by hydrolysis of phospholipids and activation of protein kinase C. Science,1992,258:607
[64]Williams B, Schrier RW.Glucose-induced protein kinase C activitityregulates arachidonic acid release and eicosanoid . production by cultured glomerular mesangial cells.) Clin Invest, 1993,92:2889
[65]Sharma K, Jin Y, Guo J. Neutralization of TGF-} antibody attenuates kidney hypertrophy and the enhanced extracellular matrix. geneexpression in STZ-induced diabete mice. diabetes,1996,45:522
[66]Messina JL, Standaert ML. Ishizuka T. Role of protein kinase C in insulin's regulation of c-fos transcription. J Biol Chem,1992, 267:9223
[67]Sharma K, Danoff V, Depiero A. Enhanced expression of inducible nitric oxide synthase in murine macrophages and glomerular
mesangial cells by elevated glucose levels:possible mediation via protein kinase C.Biochem Biophys Res Commun,1995,207:80
[68]Craven PA, Studer RK, Derubertis FR. Impaired nitric oxide-dependentcGMP generation in glomeruli from diabetic rats. J Clin Invest,1994,93:311
[69]Fukui M, Nakamura T, Ebihara Ⅰ. ECM gene expression and its modulation by insulin in diabetic rat s. Diabetes,1992,41:1520
[70]Sharma K, Jin Y, Guo J. Neutralization of TGF-} antibody attenuates kidney hypertrophy and the enhanced extracellular matrix gene expression in STZ-induced diabete mice. diabetes,1996,45:522
[71]Messina JL, Standaert ML. Ishizuka T. Role of protein kinase C in insulin's regulation of c-fos transcription. J Biol Chem,1992, 267:9223
[72]Xia P, Kramer RM, King GL. Identification of the mechanism for the inhibition of Na, K-ATPase by hyperglycemia involving activation of protein kinase C and cytolic phospholipase A2.J Clin Invest,1995 96:733
[73]KellyDJ, Zhang Y, HepperC, et al. Kinase C beta inhibition. Am J Kidney Dis,2003,42:456-465.
[74]Ahmad FK, He Z, King GL. Moleculartargets of diabetic cardiovascular complications. Curr Drug Targets,2005,6:487— 494.
[75]W illiams M E, Tuttle KR The next generation of diabetic nephropathy therapies:an update. Adv Chronic Kidney Dis, 2005,12:212-222.
[76]Ha H,Yu MR,Choi YJ,et al.Activation of protein kinase C-delta and C-epsilon by oxidative stress in early diabetic rat kidney.Am J Kidney Dis,2001,384:$204-S207.
[77]Wolf G,Ziyadeh,FN,Stahl RA.Angiotensin II stimulates expression of transforming growth factor beta receptor type II in cultured mouse proximal tubular cells[J].JMohned,1999,77 (5):556-564
[78]Rollins BJ, Walz A, Baggiolini M. Recombinant human MCP-1/JE induces chemotaxis, calcium flux, and the respiratory burst in human monocytes.Blood.1991 Aug 15;78(4):1112-6.
[79]Wada T, Furuichi K, Sakai N, Iwatay etal. Up-regulation of monocytechemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy.Kidney Int.2000 Oct;58(4):1492-9.
[80].Mezzano SA, Droguett MA, Burgos ME, etal. Overexpression ofchemolkines, fibrogenic cytol}ines, and myofibroblasts in human membranous nephropathy.Kidney Int. 2000 Jan;57(1):147-58.
[81]Wada T, Furuichi K, Sakai N, Iwata Y, etal. Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy.Kidney Int.2000 Oct;58(4):1492-9.
[82]Mezzano SA, Droguett MA, Burgos ME, etal. Overexpression of chemolkines, fibrogenic cytolkines, and my ofibro blastsin human membranous nephropathy.Kidney Int.2000 Jan;57(1):147-58.
[83]Cooper ME.Pathogenesis, prevention, and treatment of diabetic nephropathy.Lancet.1998 Jul 18:352(9123):213-9.
[84]顾勇,赖凌云.肾素一血管紧张素系统在糖尿病肾病研究中的进展.中华肾脏病杂志,2004,3：22
[85]Van Kat JP,De Lannoy LM.Jan Danser AH,et al.Angiotensin type
1 (AT1)receptor mediated accumulation of angiotensin in tissues and its intracellular half-life in vivo.Hypertension,1997,30:42-49.
[86]Banba N, Nakamura T, Matsumura M, Kuroda H, Hattori 丫 Kasai K. Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropdthy.Kidney Int.2000 Aug;58(2):684-90.
[87].Ruiz-Ortega M, Lorenzo O, Egido J. Angiotensin III increases MCP-1 and activates NF-kappaB and AP-1 in cultured mesangial and mononuclear cells.Kidney Int.2000 Jun;57(6):2285-98.
[88].文晖,林善欢.血管紧张素受体拮杭剂颧沙坦对糖尿病大鼠肾脏的保护作用.中华内科杂志,1999,3：160.
[89].Branton MN,Kopp JB.TGF-beta and ftbrosis.Microbes Infect, 1998;1(15):1349-1365
[90]lxe HB, HaH.Plasminogen activator inhibitor-1 and diabetic nephropathy.Nephrology (Carlton).2005 Oct;10 Suppl:S11-3.
[91]KorpinenE, Teppo AM, Hukkanen L, et al. Urinary transforming growth factorpl and al-microglobulin in children and adolescents with type 1 diabetes.Diabetes
[92]Hill C, Logan A, Smith C, et al. Angiotensin conveting enzyme inhibi suppresses glomerular transforming growth factor beta receptor expression experimental diabetes in rats. Diabetologia,2001;44(4):496-500
[93]EllisD} Forest K}} Erbey J} Orchard TJ. Urinary measurement of transformer growth factor-beta and type N collagen as new markers of repinjury:application in diabetic nephropathy. Clin Chem,1998;44(5):950-956
[94]荆春艳,叶山东,陈燕等糖尿病患者尿转化生长因子131检测的临床意义安徽医科大学学报,2003；38(3)：202-204
[95]ShanlandSJ} Scholey Jw. Expression of transforming growth factorBI during diabetic renal hypertrophy.Kidney Int,1994:46:430-436
[96]Bertoluci MC. Transforming growth factor B in the development of rat diabetic nephropathy. A 10-month study with insulin-treated rats. Nephron,1996; 10(9):1891-1899
[97]Yagi K, Kim S, Wanibuchi H. Characteristics of diabetes, blood pressure, and cardiac and renal complications in Otsuka Long-Evans Tokushima Fattyrats [J]. Hypertension,1997,29 (3):728-735
[98]Schafer S, Linz W, Bube A, et al. Vasopeptidase inhibition prevents nephropa -thy in Zucker diabetic fatty rats [J].CardiovascRes,2003,60(2):447-454
[99]Yagi K, Kim S, Wanibuchi H. Characteristics of diabetes, blood pressure, and cardiac and renal complications in Otsuka Long-Evans Tokushima Fattyrats [J]. Hypertension,1997,29 (3):728-735
[100]Pavan MV, Ghin B, Castro M, et al. Prevention of hypertension atten-uates albuminuria and renal expression of fibronectin in diabetic spont-aneously hypertensive rats [J]. AmJNephrol,2003,23(6):422-428
[101]Gross ML, Ritz E, Schoof A, et al. Comparison of renal morphology in the streptozotocin and the SHR/N-cp models of diabetes [J].Lablnvest,2004,84:452-464
[102]Raz I, Wexler I, Weiss O, et al. Role of insulin and the IGF system in renal hypertrophy in diabetic Psammomys obesus (sand rat) [J].Nephrol Dial Transplant,2003,18(7):1293-1298
[103]Cusumano AM, Bodkin NL, Hansen BC, et al. Glomerular hyper-trophy is associated with hyperinsulinemia and precedes overt
diabetes in aging rhesus monkeys [J]. Am J Kidney Dis,2002,40 (5):1075-1085
[104]Kelly DJ, Wilkinson-Berka JL, Allen TJ, et al. A new model of diabetic nephropathy with progressive renal impairment in the transg-enic (mRen-2)27 rat (TGR)[J]. Kidney Int,1998,54:343-352
[105]Wogensen L, Nielsen CB, Hjorth P, et al. Under control of the renal promoter, locally produced transforming growth factor-betal induces accumulation of glomerular extracellular matrix in transgenic mice [J]. Diabetes,1999,48(1):182-192
[106]Yamamoto Y, Kato I, Doi T, et al. Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice [J]. JClin Invest,2001,108:261-268
[107]北京制药工业研究所.川芎嗪有效成分的研究-川芎嗪的提取、分离和结构鉴定[J].中华医学杂志,1977,57(7)：420.
[108]北京制药工业研究所.川芎嗪有效成分的研究-川芎嗪的药理研究[J].中华医学杂志,1977,57：464.
[109]曾健英,罗正茂,张建林.川芎嗪治疗糖尿病肾病68例.广东医学,2005,26(7)：1004-1005
[110]赵秀珍,川芎嗪针剂对早期糖尿病肾病疗效观察.医药论坛杂志,2004,25(6)：31-33
[111]崔哲,陈馥,谷素洁,等.川芎嗪对老年糖尿病肾病病人肾功能及血脂的影响.人民军医,2006,49(4)：190-191
[112]赵秀珍.川芎嗪针剂对早期糖尿病肾病疗效观察[J].医药论坛,2004；25(6)：31-32
[113]阮颖新,李丽英,陈云波,等.1型糖尿病与2型糖尿病血脂变化比较[J].哈尔滨医科大学学报,2004；38(1)：94-95
[114]杨巧芝,吕学云,于爱菊.川芎嗪对肾病综合征血脂及载脂蛋白的变化的临床研究[J].中国当代儿科杂志,2002；4(6)：491-492
[115]王玉良.川芎嗪对心血管组织的药理和电生理作用-一种新的钙拮抗剂[J]．中西医结合杂志,1985,5(5)：291.
[116]Bianchis, Bigazzi R, Canpese V. Micralbuminuria in essential hypertension [J]. Am J Kidney Dis,1999:34:973
[117]王力宁,糖尿病肾病的非血液净化治疗[J].肾脏病与透析肾移植杂志,2003,12(5)：443
[118]梁锋,赵敏毅.洛汀新和葛根素治疗糖尿病肾病的临床疗效[J].实用医技杂志,2006,13(4)：544
[119]陈淑娇,郑京.ACEl、ARB阻止糖尿病肾病发展的机制[J].现代实用医学,2004,16(12)：741
[120]熊燕,贾汝汉.肾素-血管紧张素系统在糖尿病肾病发病机制中的新认识.中国中西医结合肾病杂志,2004,5(9)：553～555
[121]Li C, Yana CW.Park CW.et al. Long-term trealment w ith ramipril auenuales renal osleoponlin expression in diahelic rats. Kidney Inl, 2003,63(2):454-463
[122]邢淑丽,郑君芙,黄文政.单侧肾切除STZ诱导糖尿病肾病大鼠动物模型研究.中国中医急症杂志,2006；(15)6：643-644
[123]顾明,邵凤民.肾小管间质纤维化机制的研究进展.医药论坛杂志,2005,26：(5)70-73
[124]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)：811-814
[125]冯建春,倪青.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)：212-214
[126]宫伟星,姜新国,王俊基,等.糖肾通宝饮治疗早期糖尿病肾病的临床研究[J].山东中医药大学学报,2000,24(2)：111-113
[127]于淼.糖尿病肾病中药复方实验研究进展[J].长春中医学院学报,2004,20(1)：57-59
[128]谢席胜.糖尿病肾病单味中药研究进展[J].中医药研究,2002,18(6)：47-48
[129]邵倩,陈福琴.川芎嗪在糖尿病肾病中的应用及其机制研究.中国中西医结合肾病杂志,2002,3(12)：739-741
[130]于淼.糖尿病肾病中药复方实验研究进展[J].长春中医学院学报,2004,20(1)：57-59
[131]翁孝刚,郭永年,王道刚,等.川芎嗪治疗糖尿病慢性并发症.新乡医学院学报；1993,10(3)：187.
[132]唐诗伟,朱红倩,晏永慧,等.川芎嗪治疗2型糖尿病肾病38例观察.实用中医药杂志,1999,15(8)：3-4
[133]顾碧云,戴晓星,张允亭,等.川芎嗪对糖尿病血液高凝状态的影响[J].中西医结合杂志,1989,9(5)：320
[134]吴建平,沈世忠,杨忠民.川芎嗪对肾病综合征肾功能、血脂及血液流变学的影响[J].中华肾脏病杂志,1999,15(3)：169
[135]熊旭明,梁剑波,潘巧红,等.尿视黄醇结合蛋白与糖尿病肾病.中华肾脏病杂志.1997,13(4)：215
[136]杨沛,陈伟,姚春燕.糖尿病肾病的早期诊断.中国现代医学杂志.2002,3(5)：48-50
[137]陈海英，沈稚舟.2型糖尿病病人微量白蛋白的影响因素.中国实验诊断杂志.1998,2(1)：18-21
[138]LiC,Yang Park renalosteopont in expression etal.Long-term treatment with ramipril attenuates in diabetic rats. Kidney Int,2003, 63:454-463
[139]Abdel-Wahab N, Yevdokimova N,Weston BS etal. Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy. BiochemJ,2001;359(1):77-87
[140]张卫平.浅谈活血化瘀法在糖尿病肾病治疗中的运用.实用中医药杂志,2003,19(5)；268
[141]Wada T,Furuichi K,Sakai N, et al.Gene therapy via blockade of monocyte chemoattractant protein-1 for renal fibrosis. J Am Soc Nephrol,2004,15:940-948.
[142]Panzer U,Thaiss F,Zahner G,et al. Monocyte chemoattractant protein-1 and osteopontin differentially regulate monocytes recruitment in experimential glomerulonephritis.Kidney Int,2001,59 (5):1762-1769.
[143]于世鹏,郭焕,王雪等.楠糖尿病肾病患者MCP-1和OPN变化及意义[J].山东医药,2007,47(28)：46-47.
[144]刘国元.TGF-β1与肾小球硬化关系的研究[J]国外医学泌尿系统分册,2002,22(6)：361-363
[145]Li JH, Zhu HJ, Huang XR, et al. Smad 7 inhibits fibrotic effect of TGF-beta on renal tubular epithelial cells by blocking smad2 activation [J].J Am Soc Nephrol,2002,13:1464-1472.
[146]Koya D, King Gl.. Protein kinase C activation and the development of diabetic complications. Diabetes.1998:47:859-866
[147]Haneda M, Koya D, Kikkawa R. Cellular mechanisms in the development and progression of diabetic nephropathy:activation of the DAG-PKC-ERK pathway. Am J Kidney Dis.2001:38(4 Suppl 1):S178-81
[148]Ways DK, Sheetz MJ. The role of protein kinase C in the development of the complications of diabetes. Vitam Horm.2000;60:149-93
[149]Whiteside Cl, Dlugosz JA. Mesangial cell protein kinase C isozyme activation in the diabetic milieu. Am J Physiol Renal Physiol 2002 Jun;282 (6):F975-80
[150]吴永贵,林善琐.蛋白激酶C与糖尿病肾病.中华肾脏病杂1998；14(6)399-402
[151]RaptisAE, VibertiG.Pathogenesis of diabetic nephropathy. ExpClin Endocrinol Diabeties 2001:109 (suppl2):5424-437
[152]Ganz M, Saxena R, Hawkins K, et al. PDGF and IL-1 induce and activate specific protein C isoforms in mesangial cells. Am J Physiol Renal Fluid Electrolyte Physiol 1996:271:F108-F113
[153]Pfaff IL, Vallon V. Protein kinase C beta isoenzymes in diabetic kidneys and their relation to Nephroprotective actions of the ACE inhibitor Lisinopril. Kidney Blood Presss Res 2002:25:329-340
[1]Anderson AR, et al. Diabetic nephropathy in type 1 (insulin-dependent) diabetes:An epidemiological study. Diabetologia, 1983,23 B496
[2]孙建红,何戎华,任传路.虫草制剂和开博通对糖尿病大鼠肾脏功能和形态影响的对比研究.徐州医学院学报,2000,20(6)：450-453
[3]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.现代中医药,2007,27(3)：69-71
[4]艾智华,蔡红卫,张忠辉.大黄酸治疗大鼠糖尿病肾病的实验研究.第三军医大学学报,2004,26(4)：304-306
[5]柴可夫,柴瑞.糖肾汤对糖尿病大鼠肾脏保护作用的实验研究.中医药学刊,2005,23(9)：1551-1552
[6]李佑生,王文健,马宇滢,等.复方丹参滴丸防治大鼠早期糖尿病肾脏损害的研究.中成药,2007,(1)：40-44
[7]张莹雯,谢丹,杜光,等.归芪方合苯那普利对糖尿病大鼠肾组织转化生长因子β1的影响.中国中西医结合杂志,2005年6月第25卷基础理论研究特集86～90
[8]朱国茹,石岩,马丽佳.糖肾保煎剂和雷米普利对糖尿病大鼠肾脏保护作用的对比实验.中国中医药信息杂志,2005,12(1)：30-32
[9]苏小惠.中西医结合治疗糖尿病肾病40例临床观察.辽宁中医杂志.2006,33(1)：92-93
[10]王国芝,张莉,屈云.糖尿病肾病的中西医结合治疗的临床研究[]].现代中医药,2003,(4)：36-38
[11]张焱.中西医结合治疗糖尿病肾病30例的临床观察.生临床和实验医学杂志.2006,5(4)：402-403
[12]陈望善,杨玉霞,李华.中西医结合治疗糖尿病肾病的临床观察.湖北中医杂志.2004,26(12)：9-10
[13]胡宝峰,李秋英,任小强,等.补阳还五汤加味治疗早期糖尿病肾病56例.陕西中医,2005,26(12)：1281-1282
[13]林楠,宋王宣,薛丽.通心络胶囊治疗糖尿病肾病疗效观察.中国误诊学杂志.2005,5(9)：1663-1664
[14]宋晓燕,陈蔷,齐晓燕.六味地黄丸对早期糖尿病肾病患者红细胞醛糖还原酶活性的影响.中国中西医结合杂志.2004,24(12)：1087-1090
[15]陈弼沧,吴秋英.血府逐瘀口服液治疗糖尿病肾病的临床观察.吉林中医药.2003,23(1)：15-16
[17]尹红梅.川芎嗪与山莨菪碱治疗糖尿病肾病40例.临床荟萃.2000,15(12)：553-554
[18]黄各宁,陈积优,张镁元.灯盏花素注射液对糖尿病肾病血液流变学影响的临床研究.新.2006,38(3)：34-35
[19]杨益芳.葛根素注射液治疗50例糖尿病肾病的疗效观察.泸州医学院学报.2003,26(1)：44-45
[20]曹骥翔,唐新玉,丁亮,等.黄芪、生脉注射液联合苯那普利治疗糖尿病肾病32例疗效观察.湖南中医药导报.2002,8(10)：596-597
[21]杨燕,邸阜生,李坤.静黄芪丹参注射液与开博通联合应用治疗糖尿病肾病.临床观察天津医科大学学报.2000,6(1)：79-81
[22]史伟,唐爱华,吴金玉,等.水蛭注射液治疗糖尿病肾病57例疗效观察.新中医.2006,38(3)：38-40
[23]马为,唐桂军,郭泉滢.杏丁注射液治疗糖尿病肾病52例.中医研究.2004,17(2)：31-32
[24]刘香春.中药灌肠法治疗糖尿病肾病肾功能不全30例.四川中医．2006,24(4)：68-69
[25]王秀霞,李富英.中药灌肠合灸神厥穴对糖尿病晚期肾病的影响.山东医药.2006,46(28)：72