通络益肾滋阴方对DN大鼠血清TGF-β_1、HGF影响的实验研究
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摘要
目的
     通过观察“通络益肾滋阴方”对糖尿病肾病(DN)模型大鼠一般情况,空腹血糖,肾脏肥大指数,24小时尿蛋白定量,肾功能(血清尿素氮、肌酐),血清TGF-β1、HGF含量的影响,以证实通络益肾滋阴方对DN大鼠的治疗效果,并从抗肾纤维化角度探讨其作用机理。
     方法
     在50只健康雄性SD大鼠中随机选取8只作为假手术对照组(简称正常对照组);其余42只行左侧肾脏切除术+STZ腹腔注射诱导复制DN模型。将36只成模大鼠随机分为3组,即病理模型对照组(简称病理对照组),通络益肾滋阴方治疗组(简称中药治疗组),洛汀新+糖适平治疗组(简称西药治疗组),分别灌胃给药10周。共观察12周,12周末检测24h小时尿蛋白定量,空腹血糖,肾功能(血清尿素氮、血肌酐),测定血清TGF-β1、HGF含量,并称重计算肾脏肥大指数(肾重/体重),光镜观察肾脏病理变化。
     结果
     经通络益肾滋阴方治疗10周后,大鼠体重较病理对照组明显增加,P<0.05;空腹血糖、肾肥大指数均较病理对照组明显降低,P<0.01;24h尿蛋白定量、血清尿素氮、肌酐均较病理对照组明显减低,P<0.01;肾组织病理损伤明显减轻;大鼠血清TGF-β1表达较病理对照组显著下调,HGF表达增加,P<0.01。
     结论
     通络益肾滋阴方对DN模型大鼠具有一定的治疗作用,其机制可能是通过降低空腹血糖,减少24h尿蛋白,抑制实验性DN大鼠血清中致纤维化因子TGF-β1的表达,延缓肾脏保护因子HGF的下降,促进HGF表达来抑制细胞外基质的积聚,从而保护肾功能,防止肾组织纤维化。
Objective
     Through observing the effect of Tongluoyishenziyinfang (TLYSZYF) on the general things, fasting blood glucose, kidney weight, index of kidney hypertrophy (kidney weight/body weight), kidney function(serum creatinine, blood urea nitrogen),the urine micro-albumin protein in 24hours (24hmAlb),expression of the serum Transforming Growth Factor-β1(TGF-β1) and Hepatocyte Growth Factor (HGF)of the DN model big rat. To validate the curative effect and investigate acting mechanism of TLYSZYF for diabetic nephropathy(DN) from the aspect of anti-fibrosis.
     Methods
     8 rats were selected for sham-operation group randomly in the fifty clean healthy male Sprague-Dawley rats, brief named normal control group. Others were had left kidney nephrectomy and intraperitoneal injected the streptonzocin (STZ) to induced diabetic nephropathy. Thirty-six diabetic nephropathy model rats were randomly divided into: pathology group, TLYSZYF group (brief named Chinese medicine group),Lostensin+Gliguidone group(brief named western medicine group).Cured for 10 weeks, This experimental altogether 12 weeks, after 12 weeks, we measured 24hmAlb,tested the fasting blood glucose, examined the blood urea nitrogen (BUN),serum creatinine(Scr),measured the expression of the serum Transforming Growth Factor-β1(TGF-β1) and Hepatocyte Growth Factor(HGF),the left kidneys were harvested to weight, calculated index of kidney hypertrophy, observe the renal pathological changes.
     Results
     After treatment of TLYSZYF, the avoirdupois of mouse was increased compared with pathology group (P<0.05);the fasting blood glucose,24hmAlb,Scr,BUN and index of kidney hypertrophy were reduced compared with pathology group (P<0.01),and renal damage eased, the expression level of the serum Transforming Growth Factor-β1 (TGF-β1) was lower, and Hepatocyte Growth Factor(HGF) was higher(P<0.01).
     Conclusion
     TLYSZYF can protect the kidney of diabetic nephropathy(DN) rats, The probable mechanism was to lower the fasting blood glucose,24hmAlb,suppress the expression of TGF-β1 in big mouse blood serum which cell factor can causes the fibrosis, delay kidney protection factor of HGF dropping and promote the expression of HGF, so TLYSZYF can decrease glomeruli extracellular matrix ingredient depositing, delay the thickening basal lamina of glomeruli and delay the process of DN.
引文
[1]吴永贵,林善锬,周江华等.苯那普利对糖尿病大鼠肾小管-间质损伤的保护作用及机制[J].中华内分泌代谢杂志,2003;19(5):406~407.
    [2]郭啸华,刘志红,李恒等.高糖高脂饮食诱导的 2 型糖尿病大鼠模型及其肾病特点[J].中国糖尿病杂志,2002;10(5):290~294.
    [3]Forbes JM,Cooper ME,Thallas V, et al. Reduction of the accumulation of advanced glycation end products by ACE inhibition in experimental diabetic nephropathy [J].Diabetes, 2002;51(11):3274~3282.
    [4]Forbes JM, Cooper ME, Thallas V,et al.Reduction of the accumulation of advanced glycation end products by ACE inhibition in experimental diabetic nephropathy [J]. Diabetes,2002;51(11):3274~3282.
    [5]Mumtaz FH,Dashwood MR,Khan MA,et al.Down-regulation of nitric oxide synthase in the diabetic rabbit kidney:potential relevance to the early pathogenesis of diabetic nephropathy[J].Curr Med Res Opin,2004;20 (1):1~6.
    [6]张芳林,李果,刘优萍等.2 型糖尿病大鼠模型的建立及其糖代谢特征分析[J].中国实验动物学报,2002;10(1):16~20.
    [7]Junod A,Lambert AE, Orci L,et al.Studies of the diabetogenicaction of streptozotocin[J].Proc Soc Exp Biol Med,1967;126:201.
    [8]何晓峰,刘晓城,邵菊芳.实验性糖尿病大鼠早期肾脏结构功能的改变[J].中华实用医学,2002;4(13):14.
    [9]杨亦彬,张翥,苏克亮等.链脲佐菌素诱导大鼠糖尿病肾病模型的方法学探讨[J].华西医学,2005;20(2):299.
    [10]高苹,贾汝汉,王学玉.厄贝沙坦对 2 型糖尿病大鼠肾组织中核因 2-κB 的调节[J].中华肾脏病杂志,2002;18(5):364.
    [11]郭啸华,刘志红,李恒等.高糖高脂饮食诱导的 2 型糖尿病大鼠模型及其肾病特点[J].中国糖尿病杂志,2002;10(5):290~294.
    [12]徐颖,周世文,汤建林等.实验性糖尿病肾病大鼠模型建立及优化[J].第三军医大学学报,2006;28(22):2247.
    [13]马骥,张汝忠.阻断 T 型钙通道可减轻糖尿病大鼠的蛋白尿肾病理改变[J]. 中华肾脏病杂志,2000;16(2):93~97.
    [14] Wada J,Zhang H, Tsuchiyama Y,Hiragushi K,Hida K,Shikata K,Kanwar YS, Makino H.Gene expression profile in streptozotocininduced diabetic mice kidneys undergoing glomerulosclerosis [J].Kidney Int,2001;59 (4):1363~1373.
    [15] OLIVETTIG,ANVERSA P,RIGAMONTIW, et al Morphometry of the renal corpuscle during normal postnatal growth and compensatory hypertrophy A lightm icro scope study[J].J CellBiol,1977;75(2 Pt1):573~585.
    [16]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[J].中国中医急症,2006;15(6):643.
    [17]王新.唐方.单侧肾脏结扎术+链脲佐菌素诱导糖尿病肾病动物模型建立方法的探讨[J].天津医科大学学报,2006;12(1):18.
    [18]宋恩峰,刘晶晶,贾汝汉等.2 型糖尿病肾病大鼠模型制备研究[J].实用医学杂志,2007;23(18):2840.
    [19]Maeda M,Yabuki A ,Suzuki S,et al .Renal lesions in spontaneous insulin – dependent diabetes mellitus in the nonobese diabetic mouse:acute phase of diabetes [J].Vet Pathol,2003;40(2):187~195.
    [20]Cohen MP,Sharma K,Guo J,et al.The renal TGF-beta system in the db/db mouse model of diabetic nephropathy [J].Exp Nephrol,1998;6(3):226~233.
    [21]Janssen U,Phillips AO,Floege J.Rodent models of nephropathy associated with type Ⅱ diabetes [J].J Nephrol,1999;12 (3):159~172.
    [22]Osterby R, Gundersen HJ.Glomerular size and structure in diabetes mellitusⅠ. Early abnormalities [J].Diabetologia,1975;11(3):225~229.
    [23]Janssen U,Vassiliadou A,Riley SG,et al.The quest for a model of type Ⅱ diabetes with nephropathy:the Goto Kakizaki rat [J].J Nephro,2004;17(6):769~773.
    [24] Sato N,Komatsu K,Kurumatani H.Late Onset of Diabetic Nephropathy in Spontaneously Diabetic GK Rats [J].A J Nephrol,2003;23(5):334~342.
    [25] Schafer S,Linz W,Bube A,et al.Vasopeptidase inhibition prevents nephropathy in Zucker diabetic fatty rats[J].Cardiovasc Res,2003;60 (2):447~454.
    [26]Pavan MV,Ghin B,Castro M, et al.Prevention of hypertension attenuates albuminuria and renal expression of fibronectin in diabetic spontaneously hypertensive rats[J].Am J Nephrol,2003;23 (6):422~428.
    [27]Gross ML,Ritz E,Schoof A,et al.Comparison of renal morphology in the streptozotocin and the SHR/N-cp models of diabetes[J].Lab Invest,2004;84:452~464.
    [28]Janssen U,Phillips AO,Floege J.Rodent models of nephropathy associated with type Ⅱ diabetes [J].J Nephrol,1999;12 (3):159~172.
    [29]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.
    [30]Cusumano AM,Bodkin NL,Hansen BC,et al.Glomerular hypertrophy is associated with hyperinsulinemia and precedes overt diabetes in aging rhesus monkeys[J].Am J Kidney Dis,2002;40(5) :1075~1085.
    [31]Nobrega MA,Fleming S,Roman RJ,et al.Initial characterization of a rat model of diabetic nephropathy[J].Diabetes,2004; 53:735~742.
    [32]Kelly DJ, Wilkinson-Berka JL, Allen TJ,et al.A new model of diabetic nephropathy with progressive renal impairment in the transgenic (mRen-2) 27 rat (TGR) [J]. Kidney Int,1998; 54 : 343~352.
    [33]Wogensen L,Nielsen CB,Hjorth P,et al.Under control of the Renlc promoter, locally produced transforming growth factor-beta1 induces accumulation of glomerular extracellular matrix in transgenic mice [J].Diabetes,1999;48(1):182~192.
    [34]Yamamoto Y,Kato I,Doi T,et al.Development and prevention of advanced diabetic nephropathy in RAGE-overexpressing mice [J].J Clin Invest,2001;108:261~268.
    [35]Trachtman H,Futterweit S,Pine E,et al.Chronic diabetic nephropathy:role of inducible nitric oxide synthase [J].Pediatr Nephrol,2002;17(1):20~29.
    [36]Hammad SM,Hazen-Martin DJ,Sohn M,et al.Nephropathy in a hypercholestero- lemic mouse model with streptozotociv-induced diabetes[J].Kidney Blood Press Res, 2003;26 (526):351~361.
    [37]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):212~215.
    [38]杨敏,张丽芬,赵进喜等.黄芪卫矛合剂对糖尿病肾病大鼠血清 LN Ⅳ型胶原含量影响[J].辽宁中医杂志 ,2007;34(3):373.
    [39]吴以岭,魏聪,王宏涛等.通肾络胶囊对糖尿病肾病大鼠肾脏细胞外基质成分及代谢的影响[J].中国中西医结合杂志,2007;27(4):326.
    [40]董正华,李小会,曹广顺等.通络益肾汤对联脲佐菌素DN大鼠疗效的实验研究[J].陕西中医学院学报,2006;29(4):40~42.
    [41]李小会,董正华,曹广顺等.通络益肾汤对链脲佐菌素诱导糖尿病肾病大鼠血浆一氧化氮影响的实验研究[J].时珍国医国药,2006;17(8):1399.
    [42]董正华,李小会,曹广顺等.通络益肾汤对联脲佐菌素DN大鼠血浆NO影响的实验研究[J].陕西中医,2006;26(6):757~759.
    [43]高国丽,车光升,董瑶等.中药益肾活血方剂抗糖尿病肾病的实验研究[J].中国医疗前沿, 2007;1(3):1.
    [44]米庆海.愈糖益肾胶囊治疗糖尿病肾病的实验研究[J].中医药学刊,2006; 24(12):2302。
    [45]常风云,赵玉庸,张金虎等. 二黄糖肾康对糖肾病大鼠肾脏保护作用的研究[J].辽宁中医杂志,2008;35(1):144~145.
    [46]常风云,成秀梅,李立等.二黄糖肾康对糖尿病肾病模型大鼠肾脏细胞凋亡及 Bax Bcl-2 表达的影响[J].中国老年学杂志,2007;27(5):439~441.
    [47]张建文,许琛珂,李迎霞.中药复方糖肾康对实验性糖尿病大鼠肾组织中TNF-αmRNA 表达的影响[J].光明中医,2006;21(3):58.
    [48]李海军,王晓光.补脾肾活血法防治糖尿病肾病的实验研究[J].山东中医杂志, 2003;22(10):618.
    [49]王锦鸿,陈仁寿.临床实用中药词典[M],北京:金盾出版社,2003,第一版:680,45,25,223,322,593.
    [50]文丹,张金早.黄芪注射液治疗糖尿病肾病临床观察[J].中国中医急症,2004;13: 369.
    [51]刘运明,曹昉睿.黄芪丹参注射液治疗早期糖尿病肾病的临床观察[J].现代医药卫生,2007;23(9):1302.
    [52]王光浩,张敬芳,杨雪琴.黄芪注射液治疗糖尿病肾病的实验研究[J].微循环学杂志,2007;17(1):20~21.
    [53]侯雁,于世家.大黄醇提物对糖尿病大鼠胰岛素敏感性及脂肪细胞因子影响的研究[J].实用糖尿病杂志,2006;2(3):45.
    [54]刘伦志,宁建平,恩施.大黄酸对糖尿病大鼠肾小管上皮细胞表型转化的影响[J].内科急危重症杂志,2007;13(1):33.
    [55]郭啸华,刘志红,王建平等.大黄酸对 NOD 小鼠糖尿病肾病治疗作用观察[J].肾脏病与透析肾移植杂志,2002;11(1):11~16.
    [56]黄燕飞,刘志红,陆惠萍等.大黄酸罗格列酮对db/ db糖尿病小鼠代谢紊乱肾脏损伤的作用比较[J].肾脏病与透析肾移植杂志,2004;13(3):215~221.
    [57]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[J].第三军医大学学报,2004;26(4):304~306.
    [58]Mao CP, Gu ZL.Puerarin reduces increased c-fos, c-jun,and type Ⅳ collagen expression caused by high glucose in glomerular mesangial cells[J]. Acta Pharmacol Sin,2005,26 (8):982~6.
    [59]吴合林,张荣英,李强翔等.葛根素对糖尿病肾病大鼠纤维连接蛋白表达的影响[J].中药药理与临床,2007;23(1):18.
    [60]李强翔,钟惠菊,李剑欣等.葛根素对糖尿病肾病大鼠细胞间黏附分子-1 基因表达的调控[J].中国医师杂志,2006;8(11):1480.
    [61]李强翔,王彩云,贺金莲等.葛根素调节糖尿病肾病大鼠降钙素相关肽的研究[J].中国微循环,2007;11(1):33.
    [62]李强翔,贺金莲,王彩云等.葛根素对糖尿病肾病大鼠 8-异前列腺素 F2α 的影响[J].中国老年学杂志,2007;27(1):108.
    [63]王宓,樊均明,刘欣颖.三七总皂甙对 IL-1α 诱导大鼠肾小管细胞转分化的影响[J].中国中西医结合杂志,2004;24(8):722.
    [64]刘海燕,陈孝文,刘华锋等.三七总苷对尿毒血清诱导的人肾小管上皮细胞TGF-β1 、CTGF 基因表达蛋白分泌的影响[J].中国药理学通报,2005;21(11): 1366~70.
    [65]刘海燕,陈孝文,刘华锋等.三七总苷对尿毒血清诱导的人肾小管上皮细胞外基质分泌及降解的影响[J].中草药,2006;37(2):245.
    [66]王战建,王书畅.冬虫夏草治疗糖尿病肾病的作用机制研究进展[J].中国中西医结合肾病杂志,2008;9(1):88~90.
    [67]吕秀芳,郭新民,王桂云.冬虫夏草对 2 型糖尿病肾病大鼠细胞凋亡的影响[J].牡丹江医学院学报,2005;26(1):22.
    [68]崔海月.冬虫夏草对糖尿病肾病大鼠肾损伤的保护作用研究[J].延边大学医学学报,2006;29(4):252.
    [69]赵燕,刘华,杨秋萍.灯盏花素对糖尿病大鼠血 TGF-β1 及肾脏结构影响的实验研究[J].云南医药,2007;28(4):324.
    [70]杜飞,高原,王兴红等.灯盏花素治疗糖尿病大鼠血清对近段小管上皮细胞氧化应激的影响[J].中国中西结合肾病杂志,2008;9(2):168.
    [71]金李君,黄平.绞股蓝皂苷对糖尿病肾病大鼠肾组织转化生长因子β1 表达的影响[J].中华中医药学刊,2007;25(9):1922.
    [72]顾江萍,赵玲,栗德林.水蛭对糖尿病肾病大鼠内皮素-1 水平的影响[J].中成药,2007;29(10):1421.
    [73]叶山东,朱禧星.临床糖尿病学[M],合肥:安徽科学技术出版,2005,第一版:11.
    [74]林兰,郭力. 糖微康对糖尿病肾病患者血液流变学的影响[J].中国中西结合肾病杂志,2003;4(4):215.
    [75]沈庆法.中医临床肾病学[M],上海:上海科学技术文献出版社,1997,第一版:212.
    [76]Chen S, Hong SW, Lglesia sdela Cruz MC, et al1 The key role of the transforming growth facto r2beta system in t he pathogenesi of diabetic nephropathy [J] Ren Fail, 2001;23 :471.
    [77] Tamaki K, Okuda S. Ro le of TGF-beta in the progression of renal fibrosis [J]. Contrib Nephrol, 2003; 139:44~65.
    [78] Liu Y. Hepatocyte growth factor and the kidney [J] Curr Opin Nephrol Hypertens, 2002;11 (1):23~30.
    [79]李晓东.抗间质纤维化分子的研究进展[J].国外医学泌尿系统分册,2005;25(6):844~847.
    [80]陈俊明.糖尿病肾病不同时期血浆肝细胞生长因子及转化生长因子 β1 水平[J].临床荟萃,2006;21(24):1760.
    [81] 李 小 会 , 董 正 华 , 丁 辉 . 糖 尿 病 肾 病 并 因 病 机 的 探 讨 [J]. 陕 西 中 医 ,2005;26(6):552~553.
    [82]董正华,曹广顺,曹文等.通络益肾汤治疗糖尿病肾病30例[J].上海中医药杂志,2007;41(9):46
    [83]杨丽珍.中西医结合治疗糖尿病肾病 38 例疗效观察[J].新中医,1998; 30(9):11~13.
    [84]李锋.化瘀利水法治疗糖尿病肾病中医临床机制分析[J].中国中西医结合肾病杂志,2005;11(6):673~674.
    [85]吕勇,王亿平.六味地黄丸对糖尿病肾病肾损害实验指标的影响[J].世界科学技术-中医药现代化.六味地黄丸临床应用学术研究,2006;8(2):109.
    [86]张金玉,仝霞.六味地黄丸治疗糖尿病肾病 40 例[J].中国民间疗法,2006;14 (4):54.
    [87]贾书心.六味地黄丸化裁治疗糖尿病肾病[J].天津中医学院学报,2001;20(2):15.
    [88]陈景亮,凌方明.六味地黄丸对早期糖尿病肾病尿微量白蛋白的影响[J].新中医, 2004;36(12):26.
    [89]邓小敏,唐爱华,周卫惠.培哚普利合用六味地黄丸治疗早期糖尿病肾病的临床疗效观察[J].四川中医,2006;24(8):52.
    [90]冯飞,刘涛.六味地黄丸(汤)治疗糖尿病的研究进展[J].长春中医学院学报,2003; 19(1):61.
    [91]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[J].中国中西医结合杂志,2004;24(12):1087.
    [92]刘亮.六味地黄丸对糖尿病肾病肾脏保护及核因子NF -Κb影响的研究[J]. 湖南中医杂志,2007;23(4):92.
    [93]刘保林,温文清,朱丹妮等.六味地黄汤对实验动物血糖水平的影响[J].南京中医学院学报,1993;9(4): 32.
    [94]赵玲,孙培.六味地黄丸药理研究概况[J].山东中医杂志,1991;10(2):59-60.
    [95]刘保林,温文清,朱丹妮等.六味地黄汤及其组方对小鼠血糖肝糖元的影响 [J].中国中药杂志,1991;16(7):437~438.
    [96]熊曼琪.中医药高级丛书《伤寒论》[M],北京:人卫出版社,2000,第一版:280.
    [97]张又云,黄河清.抵挡汤改良方治疗早期糖尿病肾病的研究[J].现代中西医结合杂志,2002;11(21):2091.
    [98]王本祥主编.现代中药药理与临床[M],天津科教翻译出版社,2004,6,459~549
    [99]张汝学,顾国明,张永祥等.地黄低聚糖对实验性糖尿病与高血糖大鼠代谢的调节作用[J].中药药理与临床,1996;(1):14~17.
    [100]赵培西,谢艳华,王剑波等.生地降糖胶囊对糖尿病小鼠的药效学研究[J].时珍国医国药,2006;17(10):1985.
    [101]郝志奇,杭秉茜,王瑛等.山药水煎剂对实验性小鼠的降糖作用[J].中国医科大学学报,1991;22(3):118.
    [102]闵清,舒思洁,洪爱蓉等.山茱萸对糖尿病小鼠血糖组织糖原含量的影响[J].咸宁医院学学报,1999;13(1):12.
    [103]钱东生,朱毅芳,朱清.山茱萸乙醇提取液对NIDDM大鼠骨骼肌GLUT4表达影响的实验研究[J].中国中药杂志,2001;26(12):859.
    [104]李丽华,许惠琴,时艳.山茱萸环烯醚萜总苷对糖尿病大鼠肾形态学及其 Na+, K+- ATP 酶活性的影响[J].云南中医学院学报,2005;28(4):43.
    [105]许惠琴,郝海平,皮文霞等.山茱萸环烯醚萜总苷对糖尿病大鼠肾皮质糖化终产物及其受体 mRNA 表达的影响[J].中药药理与临床,2003;19(4):9.
    [106]王饮茂,刘超,赵帜平等.丹皮多糖降血糖有效成分的筛选及其作用的研究[J].中国中医基础医学杂志,2001;7(5):18.
    [107]王饮茂,洪浩,赵帜平等.丹皮多糖-2b 对 2 型糖尿病大鼠模型的作用及其降糖作用机制[J].中国药理学通报,2002;18(4):456.
    [108]俞浩,刘海鹏.丹皮多糖-2b 对大鼠早期糖尿病肾病的影响[J].中国实验方剂学杂志,2007;13(2):36.
    [109]俞浩,沈业寿,刘海鹏.丹皮多糖-2b 对糖尿病肾病大鼠肾脏保护作用及机制的研究[J].中国中医药科技,2006;13(3):177.
    [110]蔡缨,沈忠松.茯苓对老年 2 型糖尿病降糖效果观察[J].解放军预防医学杂志, 2006;24(3):198.
    [111]黄正明,陈红艳 ,魏玉萍等.泽泻不同溶剂提取物对糖尿病小鼠血糖及血液生化指标的影响[J].解放军药学学报,2006;22(6):419.
    [112]杨新波,黄正明,葛文斌.泽泻提取物对正常四氧嘧啶小鼠糖尿病模型的影响[J].中国实验方剂学杂志,2002;8(3):24~26.
    [113]曹莉,茅彩萍,顾振纶.三种中药对糖尿病小鼠胰岛素抵抗的影响[J].中国血液流变学杂志,2005;15(1):42.
    [114]Lee, H. A.Kwon S.o.Lee, H.B. Hypoglycemic action of components form red ginseng :(I).Investigation of the effect of ginsenosides from red ginseng on enzymes related to glueose metabolism in cultured rat hepatoeytes. Koryo Insam Hakhoechi,1997(21),174~186.
    [115]Kitamura, H. Mori,Y. Matsumiya,S, et al.Effect of ginseng on diabetic nephropathy in WBN/Kobrats. Diabetes Frontier, 1997;(8):388-389.
    [116]王健民,马腾骧等.人参皂甙对肾脏代偿性生长的影响[J].中华肾脏病杂志,1987;3(4):173~175.
    [117]郭望祥.大黄药理研究进展[J].江汉大学学报,2002;2(30):51.
    [118]郭美姿.大黄酸药理作用研究进展[J].《国外医学》中医中药分册,2002;24 (3):139~142.
    [119]高雅萍.大黄提取物对单纯性肥胖大鼠高胰岛素血症的作用[J].中国实验方剂学杂志,2002;6(8):30~31.
    [120]郭啸华,刘志红,彭艾等.大黄酸对Ⅱ型糖尿病肾病大鼠疗效观察[J].中华肾病杂志,2002;4(18):280.
    [121]黄全海.水蛭素对 2 型糖尿病胰岛素抵抗的影响[J].浙江中医学院学报,2005;29(4):18.
    [122]沈庆法,何立群主编.肾脏病的中医药研究进展[J].上海中医药大学出版社,2004,4,159.
    [123]仝小林.周小平.李爱国等.水蛭对糖尿病大鼠肾脏病变的防治作用及机理探讨[J].中国中医药信息杂志,2002;9(6):21~23.
    [124]朱宣芳.桃仁防己提取物对大鼠血小板聚集作用的研究[J].中医药研究,2003;9(16):44.
    [125]中国医学科学院药物研究所.中草药现代研究[M],北京:北京医科大学—中国协医科大学联会出版社,1997,415.
    [126]Qin GJ,Guo CJ, Zhai SZ,et al. Effects of glycated serumproteins on proliferation and secretion of type Ⅳcollagen of cultured rat mesangial cells. Chin J Diabetes, 2000; 8(1):40.
    [127]Studer RK, Craven PA, DeRubertis FR.Low-density lipoprotein stimulation ofmesangial cell fibronectin synthesis: role of protein kinase C and transforming growth factor-beta. J Lab Clin Med, 1995; 125(1):86
    [128]Hiratsuka N, Shiba K, Nishida K, et al. Analysis of urinary albumin, transferrin, N-acetyl-beta-D-glucosaminidaseand beta-microglobulin in patients with impaired glucose tolerance. J Clin Lab Anal, 1998; 12(6): 351.
    [129]韩晓芳,潘时中,杨立勇.血清 TGF-β1 水平与糖尿病肾病相关性研究[J].福建医药杂志,2005;27(2):116.
    [130]罗群,刘东海,陈玉冲等.糖尿病肾病患者血、尿转化生长因子-β 水平变化及其临床意义[J].临床内科杂志,2006;23(1):49.
    [131]Kane to H,Morrissey J, Klahr S.Increased expression of TGF beta1 mRNA in the obstructed kidney of rat s with unilateral ureteral ligation [J].Kidney Int, 1993; 44(2): 313.
    [132]Tamaki K, Okuda S.Role of TGF-be ta in the progression of renal fibrosis. Contrib Nephrol,2003;139: 44~65.
    [133]Oh JH,Ha H, Yu MR, et al.Sequential effects of high glucose on mesangial cell transforming growth factor-beta 1 and fibronectin synthesis[J] .Kidney Int, 1998; 54: 1872.
    [134] D′Agord Schaan B,Lacchini S,Bertoluci MC,e t a l.Increased renal GLUT1 abundance and urinary TGFβ1 in streptozotocin induced diabetic rats:implications for the development of nephropathy complicating diabetes [J].Horm Metab Res,2001;33 (11):664.
    [135]Isono M,Mogyorosi A,Han DC,et al.Stimulation of TGF-beta typeⅡreceptor by high glucose in mouse mesangial cells and in diabetic kidney [J].Am J Physiol Renal Physiol,2000;278:F830~838.
    [136]Kagam i S,Border WA,Miller DE,et al.Angiotensin Ⅱstimulates extracellular matrix protein synthesis through induction of transforming growth factor-β expression in rat glomerular mesangial cells. J C lin Invest, 1994; 93: 2431.
    [137]Hill C, Logan A, Smith C,et al.Angiotensin converting enzyme inhibitor suppresses glomerular transforming growth factor beta receptor expression in experimental diabetes in rats. Diabetologia,2001;44 (4):495~500.
    [138]Yokota J,Utsumomiya KY.Mechnism of preventive effect of HMG – CoA reductase inhibitor on diabetic nephropathy.Kidney Int,1999;71:S178~181.
    [139]Kane to H,Morrissey J,K lah r S.Increased expression of TGF-beta1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation [J].Kidney Int,1993;44 (2):313.
    [140]杜俊文,吴韬,南国珍等.2 型糖尿病肾病患者血清转化生长因子-β1、原癌基因蛋白质 c-sis 的水平及其临床意义[J].临床荟萃,2007;22(11):793.
    [141]罗群,刘东海,陈玉冲等.糖尿病肾病患者血、尿转化生长因子-β1水平变化及其临床意义[J].临床内科杂志,2006,23(1):49.
    [142]李招云,王乐见,吴晓宇.血清尿液转化生长因子β1与糖尿病肾病关系的研究[J].浙江医学,2005;27(2):95.
    [143]Chen S, Hong SW, Lglesia sdela Cruz MC, et al. The key role of the transforming growth factor-beta system in the pathogenesi of diabetic nephropathy [J] Ren Fail, 2001; 23:471.
    [144] Shama K, Ziyadeh FN.Renal hypertrophy is associated with upregulation of TGF-beta 1 gene expression in diabetic BB rat and NOD mouse. Am J Physiol Renal Physiol,1994;267(6): F1094~1100.
    [145]Sharma K,Ziyadeh FN.The emerging role of transforming growth factor-βin kidney diseases.Am J Physiol,1994;35:829.
    [146]Ina K,Kitamura H,Tat sukawa S,et al.Transformation of interstitial fibroblasts and tubulointer stitial fibrosis in diabetic nephropathy.Med Electron Microsc,2002;35: 87~96.
    [147] Eikmans M,Baelde JJ,de Heer E,et al.ECM homeostasis in renal diseases:a genomic approach [J].J Pathol,2003;2000(4):526~536.
    [148]Hoshi S,Shu Y,Yoshida F, et al.Podocyte injury promotes progressive nephropathy in zucker diabetic fatty rats [J].Lab Invest,2002;82 (1): 25~35.
    [149]Li J H,Zhu H J, Huang X R, et al.Smad 7 inhibit s fibrot ic effect of TGF-beta on renal tubular epithelial cells by blocking Smad 2 activation [J].J Am Soc Nephrol, 2002;13(6): 1464~1472.
    [150]郭啸华,刘志红,戴春笋等.大黄酸抑制 TGF-β1 诱导的肾小管上皮细胞肥大及细胞外基质产生[J].肾脏病与透析肾移植杂志,2001;10(2):101.
    [151]张悦,郭慕依.肝细胞生长因子与肾脏疾病[J].国外医学生理、病理科学与临床分册,2002;22(2):171~173.
    [152]Matsumoto K,Mizuno S,Nakamura T.Hepatocyte growth factor in regeneration, renaldisease and potential therapeutics[J].Curr Opin Nephrol Hypertens,2000; 9(4):395~402 .
    [153]Dai C,Yang J,Bastacky S,et al.Intravenous administration of hepatocyte growth factor gene ameliorates diabetic nephropathy in mice[J].JAm Soc Nephrol,2004; 15(10):2637~2647 .
    [154]Liu Y.Hepatocyte growth factor in kidney fibrosis:therapeutic potential and mechanisms of actions[J].Am J Physiol Renal Physiol,2004;287(1):F7~16.
    [155]Biswas P,Roy A,Gong R,et al.Hepatocyte growth factor induces an Endothelin-mediated decline in glomerular filtration rate [J].Am J Physiol Renal Physiol,2005;288(1):F8~15 .
    [156]Liu Y. Hepatocyte growth factor and the kidney [J].Curr Opin Nephrol Hypertens, 2002; 11(1):23~30.
    [157]Garcia-Ocana A,Takane KK,Syed MA,et al.[J].J Biol Chem,2000;275:1226~1232.
    [158]Dai CS,Li YJ,Yang JW,et al[J].J Biol Chem,2003,278:27080~27087.
    [159]Mizuno S,Kurosawa T,Matsumoto K,et al.Hepatocyte growth factor prevents renal fibrosis and dysfunction in a mouse model of chronic renal disease[J].J Clin Invest,1998;101(9):1827~1834 .
    [160]Mizuno S, Nakamura T.Am J Physiol Renal Physiol,2004; 286(1):F134-F143.
    [161]牟姗,张庆怡,倪兆慧等.肝细胞生长因子受体高糖诱导肾间质成纤维细胞中的表达及意义[J].中华肾脏杂志,2002;18(3):171~174.
    [162]Mizuno S,Matsumoto K,Kurosawa T, et al. Reciprocal balance of hepatocyte growth factor and transforming growth factor-β1 in renal fibrosis in mice [J].Kidney Int, 2000; 57(3):937~948.
    [163]程宇甫,孙喜明,李兴等.HGF 对糖尿病肾病大鼠 CTGF mRNA 及 c-metmRNA 表达的影响及意义[J].中国药物与临床,2007;7(6):444.
    [164]李兴,张木勋.HGF 对糖尿病肾病 TGF-β1 mRNA 表达的影响[J].山西医科大学学报, 2006;37(7):703.
    [165]牟姗,张庆怡,赵涵芳等.高糖刺激人肾脏成纤维细胞肝细胞生长因子 c-met 的表达及意义[J].中华内分泌杂志,2002;18(4):260~263.
    [166]Liu Y,Rajur K,Tolbert E,et al.Endogenous hepatocyte growth factor ameliorates chronic renal injury by activating matrix degradation pathways[J].Kidney Int,2000;58(5):2028~2043.
    [167]李德天,边晓慧,李颖等.肝细胞生长因子对大鼠肾小球系膜细胞表达基质金属蛋白酶及纤连蛋白的影响[J].中华肾脏病杂志,2005;21:493~494.
    [168]Dai C,L iu Y.Hepa tocyte Growth Factor Antagonizes the Profibrotic Action of TGF-β1 in Mesangia Cells by Stab ilizing Smad Transcriptiona Corepressor TGF[J].J Am Soc Nephrol,2004;15: 1402~1412.
    [169]Yo Y, Morishita R, Namamoto K, et al.Actions of hepatocyte growt h factor as alocal modulator in the kidney: potential role in pat hogenesis of renal disease[J]. Kidney International,1998;54(4):1128~1138 .
    [170]Mat sumoto K, Mizuno S, Nakamura T.Hepatocyte growth factor in renal regeneration, renal disease and potential therapeutics [J]. Curr Opin Nephrol Hypertens, 2000;9(4):395~402.
    [171]Adlers. Structure-function relationships in diabetic nephropathy; lesions and limitation [J].Kidney Int,1997;52(1):42~45.

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