龙芽葱木总皂苷对大鼠早期糖尿病心肌病及糖尿病肾病保护作用的实验研究
|
摘要
糖尿病心肌病(DCM)作为一种与高血糖有特定关系的心肌病主要表现为心功能的降低,最终导致心力衰竭,其病理改变为细胞外基质(ECM)的聚积和心肌间质重构,其致病机制复杂。心功能的降低与心肌细胞膜离子通道、钠钙交换蛋白及肌质网钙泵功能的下降以及心肌间质纤维化等有关。因此DCM早期治疗尤为重要。龙芽葱木总皂苷(total aralosides of aralia elata, TASAE)具有改善心肌缺血、缺氧、提高抗氧化酶活性增加心肌线粒体游离钙浓度的功能,而对早期糖尿病(Diabetic Mellitus, DM)大鼠心功能和结构变化的影响,国内外尚未见报道。
本研究应用心功能测定、膜片钳(patch clamp)技术,光学显微镜、电子显微镜、免疫组织化学等方法,对DM大鼠及给予龙芽葱木总皂苷后DM大鼠在体心功能、左室心肌结构、TGF-β1、CTGF以及急性分离的左室心肌细胞的L型钙通道电流(ICa-L)、瞬时外向钾电流(Ito)等进行检测,同时对各组大鼠24h尿微量白蛋白、肾功能、肾皮质TGF-β1、CTGF及肾皮质结构进行检查。结果显示:龙芽葱木总皂苷可通过L型钙通道提升DM大鼠的心功能,降低TGF-β1、CTGF在左室心肌的表达,对心肌结构的完整性具有一定保护作用。同时,还可以降低早期DM大鼠24h尿微量白蛋白含量,减少TGF-β1、CTGF在肾皮质的表达。对延缓DCM及DN的发展具有积极作用,为临床防治提供了理论依据。
Diabetic cardiomyopathy (DCM) have a special relationship with high blood glucose, the decrease of left ventricle diastolic function is the main representation in early stage, and also the decrease of left ventricle systolic function would appeared accompanying with time going on, the heart failure would happened in the end. The structural changes show that the accumulation of extracellular matrix and the reconstitution of myocardial interstitium, the pathogenesis of DCM is very complicated. Besides the myocardial fibrosis, the decreased cardiac function is also related to the functions of membrane channel protein, Sarco endo reticulum calcium ATPase. Total arasolides of aralia elata (TASAE) have the function of mitigating myocardial ischemia, improving the activity of antioxidases. But the effects of TASAE on diabetic rats hearts in the early stage has not been reported yet. Meanwhile the effects of TASAE on diabetic rat’s 24h urine microalbumin and renal cortex structure were studied.
Objectives:
1. To observe the effects of TASAE on the hemodynamic parameters, L type calcium channel currents (ICa-L), transient outward potassium currents (Ito), TGF-β1 CTGF proteins and structures changes in diabetic rat heart during the early stages.
2. To observe the effects of TASAE on renal function, 24h urine microalbumin, TGF-β1 CTGF protein and structures changes in diabetic rat kidney during the early stages .
Methods:
The hemodynamic parameters were detested by biological function system, ICa-L and Ito were detested by patch clamp technics and the TGF-β1 CTGF were detested by immunohistochemistry methods and ultrostructures were observed by electron microscope.
Results:
1. Compares with group C, LVEDP were increased and the absolute value of±dp/dtmax were decreased in group M (P<0.05). but the TASAE groups were improved (p<0.05, p<0.01); TASAE can also increase the ICa-L (P<0.01) but no effect on Ito (P<0.05), meanwhile, It can decrease the TGF-β1 and CTGF proteins expression in diabetic rat heart (P<0.01), TASAE can protect cardiac ultrostructure from damaging in early stage.
2. In group M, relative kidney weight/body weight ratio and 24h urine microalbumin were increased (p<0.05), TGF-β1 and CTGF proteins expression also increased (p<0.05,p<0.01) but they were decreased in TASAE groups (p<0.05). The quantity of mesangium increased under optical microscope and glomerular basement membrane became thicken under electron microscope in group M, but they were better in TASAE group.
Conclusions:
1.It was discovered that different pathological changes in diabetic heart and kidney at high blood glucose state by observations of morphalogical changes and hemodynamic parameters, it showed that the models of diabetic cardiomyopathy and nephropathy were sucessed.
2.It was observed that L-type calcium currents is decreased in early diabetic cardiomyocyte and TASAE can increase it,It was proved they are L-type calcium currents by Verapail and submit dose dependent.
3.It was found that diastolic function is declined at 4 weeks and both systolic and diastolic function decreased at 8 weeks,TASAE can improve it through L-type calcium currents ,also submit dose dependent.
4.Persistent high blood glucose state can improve the TGF-β1、CTGF protein expression in diabetic heart and kidney during the early stage,TASAE can inhibit it and protect the structural integrity.
5.TASAE can protect the structure of diabetic myocardium and glomerular basement membrane,lower the quantity of 24h urine microalbumin. According to the results, we suggested that they may have the common protective mechanism on diabetic heart and kidney by TASAE through inhibiting the TGF-β1、CTGF protein expression.
本研究应用心功能测定、膜片钳(patch clamp)技术,光学显微镜、电子显微镜、免疫组织化学等方法,对DM大鼠及给予龙芽葱木总皂苷后DM大鼠在体心功能、左室心肌结构、TGF-β1、CTGF以及急性分离的左室心肌细胞的L型钙通道电流(ICa-L)、瞬时外向钾电流(Ito)等进行检测,同时对各组大鼠24h尿微量白蛋白、肾功能、肾皮质TGF-β1、CTGF及肾皮质结构进行检查。结果显示:龙芽葱木总皂苷可通过L型钙通道提升DM大鼠的心功能,降低TGF-β1、CTGF在左室心肌的表达,对心肌结构的完整性具有一定保护作用。同时,还可以降低早期DM大鼠24h尿微量白蛋白含量,减少TGF-β1、CTGF在肾皮质的表达。对延缓DCM及DN的发展具有积极作用,为临床防治提供了理论依据。
Diabetic cardiomyopathy (DCM) have a special relationship with high blood glucose, the decrease of left ventricle diastolic function is the main representation in early stage, and also the decrease of left ventricle systolic function would appeared accompanying with time going on, the heart failure would happened in the end. The structural changes show that the accumulation of extracellular matrix and the reconstitution of myocardial interstitium, the pathogenesis of DCM is very complicated. Besides the myocardial fibrosis, the decreased cardiac function is also related to the functions of membrane channel protein, Sarco endo reticulum calcium ATPase. Total arasolides of aralia elata (TASAE) have the function of mitigating myocardial ischemia, improving the activity of antioxidases. But the effects of TASAE on diabetic rats hearts in the early stage has not been reported yet. Meanwhile the effects of TASAE on diabetic rat’s 24h urine microalbumin and renal cortex structure were studied.
Objectives:
1. To observe the effects of TASAE on the hemodynamic parameters, L type calcium channel currents (ICa-L), transient outward potassium currents (Ito), TGF-β1 CTGF proteins and structures changes in diabetic rat heart during the early stages.
2. To observe the effects of TASAE on renal function, 24h urine microalbumin, TGF-β1 CTGF protein and structures changes in diabetic rat kidney during the early stages .
Methods:
The hemodynamic parameters were detested by biological function system, ICa-L and Ito were detested by patch clamp technics and the TGF-β1 CTGF were detested by immunohistochemistry methods and ultrostructures were observed by electron microscope.
Results:
1. Compares with group C, LVEDP were increased and the absolute value of±dp/dtmax were decreased in group M (P<0.05). but the TASAE groups were improved (p<0.05, p<0.01); TASAE can also increase the ICa-L (P<0.01) but no effect on Ito (P<0.05), meanwhile, It can decrease the TGF-β1 and CTGF proteins expression in diabetic rat heart (P<0.01), TASAE can protect cardiac ultrostructure from damaging in early stage.
2. In group M, relative kidney weight/body weight ratio and 24h urine microalbumin were increased (p<0.05), TGF-β1 and CTGF proteins expression also increased (p<0.05,p<0.01) but they were decreased in TASAE groups (p<0.05). The quantity of mesangium increased under optical microscope and glomerular basement membrane became thicken under electron microscope in group M, but they were better in TASAE group.
Conclusions:
1.It was discovered that different pathological changes in diabetic heart and kidney at high blood glucose state by observations of morphalogical changes and hemodynamic parameters, it showed that the models of diabetic cardiomyopathy and nephropathy were sucessed.
2.It was observed that L-type calcium currents is decreased in early diabetic cardiomyocyte and TASAE can increase it,It was proved they are L-type calcium currents by Verapail and submit dose dependent.
3.It was found that diastolic function is declined at 4 weeks and both systolic and diastolic function decreased at 8 weeks,TASAE can improve it through L-type calcium currents ,also submit dose dependent.
4.Persistent high blood glucose state can improve the TGF-β1、CTGF protein expression in diabetic heart and kidney during the early stage,TASAE can inhibit it and protect the structural integrity.
5.TASAE can protect the structure of diabetic myocardium and glomerular basement membrane,lower the quantity of 24h urine microalbumin. According to the results, we suggested that they may have the common protective mechanism on diabetic heart and kidney by TASAE through inhibiting the TGF-β1、CTGF protein expression.
引文
1. Rubler S, Dulgash J. Yuceoglu Y et al. New type of Cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol, 1972,30(6):595- 602.
2. Hamby RI, Zoneraish S, Sherman L, et al. Diabetic cardiomyopathy[J]. JAMA 1974,229(13):1749-1754.
3. Ren J, Davidoff AJ. Diabetes rapidly induces contractile dysfunctions in isolated ventricular myocytes[J]. Am J Physiol, 1997,272:H140-158.
4. Davidoff AJ, Ren J, Low insulin and high glucose induce abnormal relaxation in cultured adult rat ventricular myocytes[J]. Am J Physiol, 1997,272: H159-167.
5. Okumura K, Akiyama N, Hashimoto H, et al. Alteration of 1,2-diacylglycerol content in myocardium from diabetic rats. Diabetes, 1998,37(9):1168-1172.
6. Way KJ, Katai N, King GL. Protein kinase C and the development of diabetic vascular complications. Diabet Med, 2001,18(12):945-959.
7. Way KJ, Isshiki K, Suzuma K, et al. Expression of connective tissue growth factor in increased in injured myocardium associated with protein kinase C beta 2 activation and diabetes. Diabetes, 2002,51(9):2709-2718.
8. Ramirez LC, Arauz Pacheco C, Lackner C, et al. Lipoprotein (a) levels in diabetes mellitus: relationship to metabolic control. Ann Interned 1992,117:42-47.
9. Mcneill JH. Role of elevated lipid in diabetic cardiomyopathy. Diabetes Res Clin Pract, 1996,31(suppl):S67-71.
10. Kennedy AL, Lyons TJ. Glycation, Oxidation, and Lipoxidation in the development of diabetic complication. Metabolism, 1997,46:14-21.
11. Shepherd, Ca MC, Sambandam N et al. Streptozotocin-induced diabetes enhances cardic heparin-releasable lipoprotein lipase activity in spontaneously hypertension rats[J]. Hypertension, 1998,31(8):878-884.
12. Oshima M, Higashi S, Autoradiographic study of myocardial fatty acid metebolism in diabetic mouse using 125I MPIPP[J]. Nipon Igaku Hoshasen Gakkai Zasshi, 1996,56(3):137-141.
13. Finck BN, Han X, Courtois M et al. A critical role for PPAR alpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content[J]. PNAS, 2003,100(3):1226-1231.
14. Dillmann WH. Diabetes and thyroid-hormore-induced changes in cardiac function and their molecular basis[J]. Annv Rev Med, 1989,40:373-394.
15. Hofmann PA, Menon V, Gennaway KF. Effects of diabetes on isometric tension as a function of [Ca2+] and PH in rat skinned cardiac myocytes[J]. Am J Physiol, 1995,2669:H1656-H1663.
16. Stanky WC, lopaschuk GD, Mc cormack JG. Regulation of energy substrate metabolism in the diabetic heart[J]. Cardiovasc Res, 1997,34:25-33.
17. Hsu K, Tsai L, Chiang CH, et al. Myocardial mechanics and titin in experimental insulin-resistant rats[J]. Jpn Heart, 1997,38:717-728.
18. Ligeti L, Szenczi O, Prestia CM, et al. Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy. Int Mol Med, 2006,17(6):1035-1043.
19. 心脏生理学. L.H. 奥佩著. 高天祥, 高天礼, 译. 北京: 科学出版社出版, 2001,9.
20. Perez PJ, dRamos-Franco J, Fill M, et al. Identificational and functional reconstitution of the type 2 1,4,5-trisphosphate receptor from vertricular cardiac myocytes, j Biol Chem, 1997,272:23961-23969.
21. Lompre A-M, Anger M, Levitsky D. Sarco (endo) plasmic reticulum calcium pumps in the cardiovascular system function and gene expression. J Mol Cell Cardiol, 1994,26:1109-1121.
22. Tada M, Katz Am. Phosphorylation of sarcoplasmic reticulum and sarcolemma. Annu Rev Physiol, 1982,44:401-423.
23. Hattori Y, Matsuda N, Kimura J, et al. Diminished function and expression of the cardiac Na+-Ca2+ exchanger in diabetic rats: implication in Ca2+ Overload[J]. J Physoiol, 2001,527:85-94.
24. Russ M, Reinaue H, Eckel J. Diabetes-induced decrease in the mRNA coding for sarcoplasmic reticulum Ca2+-ATPase in adult rat cardiomyocytes[J]. Biochem Biophys Res Comm, 1991,178:906-912.
25. Chattou S, Diacono J, Feuvray D. Decrease in Sodium-calcium exchange and calcium currents in diabetic rat ventricular myocytes[J]. Acta Physiol Scand, 1999,166:137-144.
26. Zhao XY, Hu SJ, Li J, et al. Decreased cardiac sarcoplasminc reticulum Ca2+-ATPase activity contributes to cardiac dysfunction in streptozotocin- induced diabetic rats. J Physiol Biochem. 2006,62(1):1-8.
27. Bidasec KR, Zhang Y, Shao CH, et al. Diabetes increases formation of advanced glycation end product on sarco (endo)plasmic Ca2+-ATPase Diabetes. 2004,53(2):463-473.
28. Schaffer SW, Ballard-croft C, Boerth S, et al. Mechanism underlying depressed Na+/Ca2+ excharger activity in the diabetic heart. Cardiovasc Res, 1997,34(1):129-136.
29. Wang DW, Kiyosue J, Shigen atsu S et a. Abnormalities of K+ and Ca2+ currents in ventricular myocytes from rats with chronic diabetes[J]. Am J Physiol, 1995,769:H1288-1296.
30. Shimoni Y, Firek L, Severson D, et al. Short-term diabetes alters K+ currents in rat Ventricular myocytes[J]. Cite Res, 1994,74:622-628.
31. Yang JM, Choic H, Ikorg KA, et al. Increased expression Galphaq protein in the heart of streptozotocin-induced diabetes rats [J]. Exp Mol Med, 1999,31(4):129-134.
32. Rodrigues B, Cam MC, MC Neill JH. Metabolic disturbances in diabetic cardiomyopathy[J]. Mol Cell Biochem, 1998,180:53-57.
33. Tanignchi N, Kaneto H, Asahi M, et al. Involvement of glycation and Oxidative stress in diabetic macroangiopathy. Diabetes, 1996,45(suppl,3): S81-83.
34. Nowri HO, Frei B, Keaney JF. Glucose enhancement of LDL oxidation is strictly metal iondependent. Free Radical Biol Med, 2000,29:814-824.
35. Kucharska J, Braunova Z, Ulcna O, et al. Dificit of coenzyme Q in heart and liver mitochondria of rats with streptozotocin-induced diabetes Physiol Res. 2000,49:411-418.
36. Brownlee M. Biochemistry and molecular cell biology of diabetic complication [J]. Nature, 2001,414(6865):813-820.
37. Cai L, Wang Y, Zhou G, et al. Attenuation by metallothionein of early cardiac death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy. J Am Coll Cardiol, 2006,48(8):1688-1697.
38. Vecchini A, Del Rosso F, Binaglia L, et al. Molecular defects in sarcolemmal glycerophospholipid subclasses in diabetic cardiomyopathy J, Mol Cell Cardiol, 2000,32:1061-1074.
39. Brown L, Wall D, Marchant C, et al. Tissue specific changes in angiotensin Ⅱreceptors in streptozotocin diabetic rats, J Endocronal, 1997,154:355.
40. Kim S, Wanibuchi H, Hamaguchi A, et al. Angiotensin blockade improvescardiac and renal complications of type II diabetic rats. Hypertension, 1997,30(5):1054-1061.
41. Fiordaliso F, Li B, Latini R, et al. Myocyte death in streptozotocin-induced diabetes in rats in angiotensin II-dependent [J]. Lab Invest, 2000,80:513-527.
42. Kajstura J, Fiordaliso F, Andreol: Am, et al. IGF-1 overpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress. Diabetes, 2001,50(6):1414-1424.
43. Fredersdorh S, Thumann C, Ulucan, C, et al. Myocardial hypertrophy and enhanced left ventricular contractility in zucker diabetic fatty rats Cardiovasc Pathol, 2004,13(1):11-19.
44. Feng Q, Lambert ML, Collow ID, et al. Venous neuropeptide Y receptor responsiveness in patients with chronic heart failure[J]. Clin Pharmacol Ther, 2000,67(3):292-298.
45. Millar BC, Plper HM, Mc Dermott BJ. The antiadrenergic effect of neuropeptide Y on the ventricular cardiomyocyte[J]. Naunyn Schmiedebergs Arch Pharmacol, 1998,338(4):426-429.
46. Mihtante JD, Lombardini JB, Shaffer SW. The role of tanrine in the pathogenesis of the cardiomyopathy of insulindependent diabetes mellitus[J]. Cardiovase Res, 2002,46(3):393-402.
47. 朱禧星, 周晓明, 何德华, 等. 链脲佐菌素糖尿病大鼠的心肌病变. 中华内分泌代谢杂志. 1992,8(4):222.
48. 周晓明, 钟学礼, 朱禧星, 等. 自发性遗传性糖尿病 BB 鼠慢性心脏超微结构病变的定量研究. 中华医学杂志, 1990,70(5):28-30.
49. Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation Study in awake chronically instrumented goats. Circulation, 1995,92(7):1954-1968.
50. Aomine M, Nobe S, Arita M. Increased susceptibility to hypoxia prolonged action potential duration in ventricular papillary muscles from diabetic rats. Diabetes, 1990,39:1485-1489.
51. Casis D, Gallege M, Iriarte M, et al. effects of diabetic cardiomyopathy on regional electrophysiologic characteristics of rat ventricular [J]. Diabetologia, 2000,43(1):101-109.
52. Pacher D, Ungvari ZJ, Nanasi PP, et al. Electrophysiological changes in rat ventricular and atrial myocardium at different stage of experimental diabetes [J]. Acta Physiol Scard, 1999,166(1):7-13.
53. Lagadic-Grossmann D, Bucker KJ, Prigent KL, et al. Altered Ca2+ handling in ventricular myocytes isolated from diabetic rats [J]. Am J Physiol, 1996, 270(5):H1529-H1537.
54. Fein FS, Kornstein LB, Strobecket JE, et al. Altered myocardial mechanics in diabetic rats. Cir Res. 1980,47:922-933.
55. Zhong M, Zhang Y, Miao Y, et al. Mechanism of reversion of myocaodial interstitial fibrosis in diabetic cardiomyopathy by valsartan. Zhong Hua Yi Xue Za Zhi, 2006,86(4):232-236.
56. Airaksinen KEJ. Effects of isometric exercise and heart rate on left ventricular filling pattern assessed by Doppler. Echocardiography. 1989,226:245-249.
1. Bradham DM, Igarashi A, Potter RL, et al. Connective tissue growth factor: a cystein-rich mitogen secreated by human vascular endothelial cells is related to the SRC induced immediate early gene product CEP 10 [J]. J Cell Biol, 1991,114(6):1285-1294.
2. Frazier K, Williams, kothapalli D, et al. Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor. J Invest Dermatol, 1996,107(3):404-413.
3. Dickmeis T, plessy C, Rastegar S, et al. Expression profiling and comparative genomics identify a conserved regulatory region controlling midline expression in the zebrafish embro. Genome Res, 2004,14(2):228-238.
4. Lau LF, Lam SC. The CCN family of angiogenic regulators the intergin connection. Exp Cell Res, 1999,248(1):44-57.
5. Segarini PR, Nesbitt JE, Li D, et al. The low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor is a receptor for connective tissue growth factor. I Biol Chem, 2001,276(44):40659-40667.
6. Nishida T, Nakanishi T, Shimo T, et al. Demonstration of reecptors specific for connective tissue growth factor on human chondrocytic cell line (HCS-2/8). Biochem Biophys Res Commun. 1998,247:905-916.
7. Wahab NA, Brinkman H, Mason RM, et al. Uptake and intracellular transport of the conneetive tissue growth factor: a potential mode of actin. Biochem J, 2001,359(pt1):89-97.
8. Yang M, Huang H, Li J, et al. Tyrosine phosphorylation of the LDL receptor-related protein (LRP) and activation of the EPK pathweay are required for connective tissue growth factor to potentiate myofibroblastdifferentiation, FASEB J, 2004,18(15):1920-1921.
9. Folger PA, Zekaria D, Grotendot G, et al. Transforming growth factor-beta-stimulated connective tissue growth factor expression during corneal myofibroblast differentiation. Invest Ophthal Mol Uis Sci, 2001,42(11):2534-2541.
10. Leask A, Holmes A, Abraham DJ. Connective tissue growth factor: a new and important player in the pathogenesis of fibrosis. Curr Pheumatol Rep 2002,4:136-142.
11. 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):213-219.
12. Chen Y, Abraham DJ, Xu shi-wen, et al. CCN2C (connective tissue growth factor) promotes fibroblast adhesion to fibronectin. Mol Biol Cell, 2004,15(12):5635-5646.
13. Chen CC, Chen N, Lan LT. The angiogenic factors Cyr61 and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts. J Biol Chem. 2001,276(13):10443-10451.
14. Shimo T, Nakanishi T, Kimura Y, et al. Inhibition of endogenous expression of connective tissue growth factor by its antisense ologonucleotide and antisense RNA suppresses proliferatin and migration of vascular endothelial cells. J Biochem Tokyo, 1998,124(1):130-136.
15. Abdel-Wahab N, Weston BS, Roberts T, et al. Connective tisssue growth factor and regulation of the mesangial cell cycle: role in cellular hypertrophy. J Am Soc Nephrol, 2002,13(10):2437-2445.
16. Cruzado JM, Ltoberas N, Torras J, et al. Regression of advanced diabetic nephropathy by hepatocyte growth factor gene therapy in rats. Diabetes,2004,53(4):1119-1127.
17. Riser BL, Denichilo M, Cortes P, et al. Regulation of connective tissue growth factor activity in cultured rat mesangial cells and its expression in experimental diabetic glomerulosclerosis. J Am Soc Nephrol, 2000,11:25-38.
18. McLennan SV, Wang XY, Moreno V, et al. Connective tissue growth factor mediates glucose effects of matrix degradation through tissue inhibitor of matrix metalloproteinase type I: implications for diabetic nephropathy. Endocrinology, 2004,145:5646-5655.
19. Kobayashi T, Inoue T, Okada H, et al. Connective tissue growth factor mediates the profibrotic effects of transforming growth factor-beta produced by tubular epithelial cells in response to high glucose. Clin Exp Nephrol, 2005,9:114-121.
20. Liu BC, Sun J, Chen Q, et al. Role of connective tissue growth factor in mediating hypertrophy of human proximal tubular cells induced by angiotensin II. Am J Nephrol, 2003,23:429-437.
21. Ruperez M, Ruiz-Ortega M, Esteban V, et al. Angiotensin II increases connective tissue growth factor in the kidney. Am J Pathd, 2003,163:1937-1947.
22. Ahmed MS, Qie E, Vinge LE, et a. Connective tissue growth factor-a novel mediator of angiotensin II-stimulated cardiac fibroblast activation in heart failure in rats. J Mol Cell Cardiol, 2004,36:393-404.
23. Zhou G, Li C, Cai L. Advanced glycation end-products induce connective tissue growth factor-mediated renal fibrosis predominantly through transforming growth factor beta-independent pathway. Am J Pathol, 2004,165:2033-2043.
24. Twigg SM, Joly AH, Chen MM, et al. Connective tissue growth factor/IGF-binding protein-related profein-2 is a mediator in the induction of fibronectin by advanced glycosylation end-products in human dermal fibroblasts. Endocrinology, 2002,143(4):1260-1269.
25. Duncan MR, Frazier KS, Abramson S, et al. Connective tissue growth factor mediates transforming growth factor beta induced collagen synthesis: down-regulation by camp. FASEB J. 1999,13:1774-1786.
26. Yokoi H, Sugawara A, Mukoyama M, et al. Role of connective tissue growth factor in TGF-beta induced fibronectin expression in rat renal fibroblasts and its upregulation in obstructive nephropathy. J Am Soc Nephrol, 2000,11:540-548.
27. Gupta S, Clarkson MR, Duggar J, et al. Connective tissue growth factor: potential role in glomerulosclerosis and tubulointerstitial fibrosis. Kidney Int, 2000,58(4):1389-1399.
28. Mori T, Kawara S, Shinozaki M, et al. Role and interaction of connective tissue growth factor with transforming growth factor beta in persistent fibrosis: A mouse fibrosis model. J Cell Physiol, 1999,18(1):153-161.
29. Hishikawa K, Oemar BS, Nakaki J, et al. Static pressure regulates connective tissue growth factor expression in human mesangial cells. J Biol Chem, 2001,276:16797-16803.
30. Liu BC, Chen Q, Luo DD, et al. Mechanisms of irbesartan in prevention of renal lesion in streptozotocin-induced diabetic rats. Acta Pharmacol Sin, 2001,276:16797-16803.
31. Lee CI, Guh JY, Chen HC, et al. Advanced glycation end-product-induecd mitogenesis and collagen production are dependent on angiotensin II and connective tissue growth factor in NRK-49F cell. J Cell Biochem, 2005,95:281-291.
32. Grothendorst GR, Rahmanie H, Duncan MR. Combinatorial signaling pathways determine fibroblast proliferation and myofibroblast differentiation. FASEB J, 2004,18:469-479.
33. Weston BS, Wahab NA, Mason RM. CTGF mediate TGF-beta induced fibronection matrix depositon by upregulating active alpha 5 beta1 integrin in human mesangial cells. J Am Soc Nephrol, 2003,14:601-610.
34. Core-Hyer E, Shegogue D, Markiewicz M, et al. TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal cells. Am J Physiol Renal Physiol, 2002,283:F707-716.
35. Lam S, Geest RN, Verhagen NA, et al. Connective tissue growth factor and IGF-1 are produced by human renal fibroblasts and cooperate in the induction of collagen production by high glucose. Diabetes, 2003,52:2975-2983.
36. Zhang C, Meng X, Zhu Z, et al. Role of connective tissue growth factor in renal tubular epithelial-myofibroblast transdifferentiation and extracellular matrix accumulation in Vitro. Life Sci, 2004,75:367-379.
37. Qi W, Twigg S, Chen X, et al. Integrated actions of transforming growth factor-betal and connective tissue growth in renal fibrosis. Am J Physiol Renal Physiol, 2005,288:F800-809.
38. Riser BL, Cortes P, DeNichilo M, et al. Urinary CCN2 (CTGF) as a possible predictor of diabetic nephropathy: preliminary report. Kidney Int, 2003,64:451-458.
39. Roestenberg P, Van Nienwenhoven FA, Wieten L, et al. Connective tissue growth factor is increased in plasma of type1 diabetic patient with nephropathy. Diabetes Care, 2004,27:1164-1170.
40. Nguyen TQ, Tarnow L, Andersen S, et al. Urinary Connective tissue growth factor excretion correlate with clinical markers of renal disease in a largepopulation of type I diabetic patient with diabetic nephropathy. Diabetes Care, 2006,29:83-88.
41. Candido R, Forbes JM, Thomas MC, et al. A breaker of advanced glycation end products attenuated diabetes-induced myocardial structural changes. Cir Res, 2003,1892(7):785-792.
42. Kerrie J, Keiji Isshiki, Kiyoshi suzuna, et al. Expression of connective tissue grwth factor is increased in injured myocardium associated with protein kinase C beta 2 activation and diabetes. Diabetes, 2002,51(9):2709-2718.
43. He Z, Way KJ, Arikawa E, et al. Differential regulation of angiotensin II-induced expression of connective tissue growth factor by protein kinase C isoforms in the myocardium. J Biol Chem. 2005,280(16):15719-19726.
44. 董志恒, 李才, 曲萌. 苯那普利对糖尿病大鼠心肌 CTGF 基因表达的影响及作用机制. 吉林大学学报 (医学版). 2004,30(4):520-523.
45. 赖鹏斌, 杨立勇, 林旭. 氟伐他汀对糖尿病大鼠心肌结缔组织生长因子表达的影响. 中国糖尿病杂志, 2006,14(3):224-226.
1. Hamby RI, Zoneraish S, Sherman L, et al. Diabetic cardiomyopathy [J]. TAMA 1974,229(13):1749-1754.
2. Lijian P, petrov V, Fagard R. Transforming growth factor-betal-mediated collagen gel concentration by cardiac fibroblasts [J]. J Renin Angiotensin Aldosterone Syst, 2003,4(2):113-138.
3. Laviades C, Varo N, Diez J. Transforming growth factorβ in hypertensives with cardiorenal damage [J]. Hypertension, 2000,36:517-522.
4. 孙卫民, 王惠琴. 细胞因子研究方法. 北京: 人民卫生出版社, 1999.
5. Mryazono K, Ichlio H, Heidin CH. Transforming growth factor-β, latent forms, binding proteins and receptors. Growth Factors, 1993,8(1):11-22.
6. Bottinger EP, Bitzer M. TGF-β signaling in renal disease [J]. J Am Soc Nephrol, 2002,13(10):2600-2610.
7. Choi ME. Mechanism of transforming growth factor-betal signaling [J]. Kidney Int Suppl, 2000,77:S53-58.
8. Yang H, Lu Y, Shen H. Influence of transfection of sense and antisense-TGF-betal gene on human pulmonary giant cell carcinoma cell proliferation. Zhong Hua Zhong Liu Za zhi, 1997,19:303-306.
9. Wieser R. The transforming growth factor-beta signaling pathway in tumorigenesis. Curr Opin Ocol, 2001,13(1):70-77.
10. Munger JS, Harpel JG, Gleizes PE, et al. Latent transforming growth factor-beta: structural features and mechanisms of activation. Kidney Int, 1997,51(5):1376-1382.
11. Blobe GC, Schiemann WP, Lodish HF. Role of transforming growth factor β in human disease. N Eng J Med, 2000,342:1350-1358.
12. Parving HH, Jacobser P. Rossing K, et al. Rossing benefits of long-term antihypertensive treatment on prognosis in diabetic Dephropathy. Kidney Int, 1996,49:1778-1782.
13. Massague J. Transforming growth factor-β family. Annu Rev Cell Biol, 1990,6:597-641.
14. Basile DP. The transforming growth factor beta system in kidney disease and repair: recent progress and future directions. Curr Opin Nephrol Hypertens, 1999,8(1):21-30.
15. Bertoluci MC, Schmid H, Lachat JJ, et al. Transforming growth factor-beta in the development of rat diabetic nephropathy. A 10-month study with insulin-treated rats [J]. Nephron, 1996,74(1):189-196.
16. Gambaro G, Ceol M, Del prete D, et al. GLUT-1 and TGF beta: the link between hyperglycaemia and diabetic nephropathy. Nephrol Dial Transplant, 2000,15(9):1476-1477.
17. Kagami S, Border WA, Miller DE, et al. Angiotensin II Stimulates extracellular matrix protein synthesis through induction of transforming growth factor-β expression in rat glomerular mesangial cells. J Clin Invest, 1994,93(6):2431-2437.
18. Campbell SE, Katwa LC. Angiotensin II stimulated expression of transforming growth factor beta-1 in cardiac fibroblasts and myofibroblasts. J Moll Cell Cardiol, 1997,29(7):1947-1958.
19. Mason RM, Wahab NA, Roger M, et al. Extracellular matrix metabolism in diabetic nephropathy [J]. J Am Soc Nephrol, 2003,14(5):1358-1373.
20. Iglesias-De La, Cruz MC, Ruiz-Torres P, et al. Hydrogen peroxide increases extracellular matric mRNA through TGF-β in human mesangial cells [J]. Kidney Int, 2001,59(1):87-95.
21. Chen S, Cohen MP, Ziyadeh FN. Amadori-glyacted albumin in diabetic nephropathy: pathophysiologic connections. Kidney Int, 2000,sep77:S40-44.
22. Kim YS, Kim BC, Song CY, et al. Advanced glycation end products stimulate collagen mRNA synthesis in mesangial cells mediated by protein kinase C and transforming growth factor-beta. J Lab Clin Med, 2001,138(1):59-68.
23. Guo M, Wu MH, Korompai F, et al. Upregulation of PKC gene and isozymes in cardiovascular tissues during early stages of experimental diabetes [J]. Physiol Genomics, 2003,12(2):139-146.
24. Cruden G, Zonca S, Hayward A, et a l. Mechanical stretch-induced fibronectin and transforming growth factor –β1 production in human mesangial cells is p38 mitogen-activated protein kinase-dependent [J]. Diabetes, 2000,49(5):655-661.
25. Everett AO, Mc Reddie AT, Fisher A, et al. Angiotensin receptor regulates cardic hypertrophy and transforming growth factor-beta1 expression [J]. Hypertension, 1994,23:587-592.
26. Brooks WW, Conrad CH. Myocardial fibrosis in transforming growth factor beta(1) heterozygous mice[J]. J Mol Cell Cardiol 2000,32(2):187-195.
27. Rerolle JP, Hertig A, Nguyen G, et al. plaminogen activator inhibitor type 1 is a potential target in renal fibrogenesis [J]. Kidney Int, 2004,58(5):1841-1850.
28. 范吴强. TGF-β1 和 Ang II 的相互作用在肾脏病中的意义. 国外医学·泌尿系统分册, 2000,20(5):536-540.
29. Sun Y, Zhang J, Zhang JQ, et al. Local angiotensin II and transforming growth factor β 1 in real fibrosis of rats [J]. Hypertension, 2000,35(5):1078-1084.
30. Li JP, Petrov V, Rumilla K, et al. Transforming growth factor betal promotes contraction of collagen gel by cardic fibroblasts through their differentiationinto myofibroblasts [J]. Methods Find EXP Clin Pharmacol, 2003,25 (2):79-86.
31. Sharma K, Ziyadeh FN. Renal hypertrophy is associated with upregulation of TGF-beta 1 gene expression in diabetic BB rat and NOD mouse [J]. Am J Physiol Renal Physiol, 1994,267(6):F1094-1100.
32. Wolf G, Ziyadeh FN. Molecular mechanisms of diabetic renal hypertrophy [J]. Kidney Int, 1999,56(2):393-405.
33. Ziyadeh FN, Han DC. Involvement of transforming growth factor-beta and its receptors in the pathogenesis of diabetic nephrology [J]. Kidney Int Suppl, 1997,60:S7-11.
34. Wolf G, Schanze A, Stahl, et al. p27 (kipl) knockout mice are protected from diabetic nephropathy: Evidence for p27 (kipl) haplotype insufficiency [J]. Kidney Int, 2005,68(4):1583-1591.
35. Akahori H, Ota T, Torita M, et al. Tranilast prevents the progression of experimental diabetic nephropathy through suppression of enhanced extracellular matrix gene expression [J]. J Pharmaco Ex Therap Therap, 2005,314(2):514-562.
36. McLennan SV, Fisher E, Martell SY, et al. Effects of glucose on matrix metalloproteinase aplasmin activities in mesangial cell: possible in diabetic nephropathy. Kidney Int, 2000,77(suppl):S81-87.
37. 韩 晓 芳 , 潘 时 中 . 转 化 生 长 因 子 β 与 糖 尿 病 肾 病 . 医 学 综 述 . 2005,11(6):509-511.
38. Iwano M, Quantification of glomerular TGF-β1 mRNA in patients with diabetes mellitus. Kidney Int, 1996,49(5):1120-1126.
39. Ina K, Kitanmura H, Tatsukawa S, et al. Transformation of intersititial fibroblasts and tubulointerstitial fibrosis in diabetic nephropathy [J]. MedElectron Microsc, 2002,35(2):87-96.
40. Li JH, Zhu HJ, Huang XR, et al. Smad7 inhibits fibrotic effect of TGF-beta on renal tubular epithelial cells by blocking Smad2 activation [J]. Jam Soc Nephrol, 2002,13(6):1464-1472.
41. Tsilibary EC. Microvascular basement membranes in diabetes mellitus. J Pathol, 2003,200(4):537-46.
42. Miyata T, Kurokawa K, et al. Relevance of oxidative and carbonyl stress to long-term uremic complications[J]. Kidney Int, 2000,58:120-125.
43. Angela G, Grit M, et al. Impact of metabolic control and serum lipids on the concentration of advanced glycation end products in the serum of children and adolescents with type 1 diabetes, as determined by fluorescence spectroscopy and N[epsilon]-(carboxymethyl) lysine ELISA[J]. Diabetes Care, 2003,26:2609-2621.
44. Copper ME, Gilbert RE, et al. Pathophysiology of diabetic nephropathy[J]. Metabolism, 1998,47 (Suppl): S3-S6.
45. 陈小瑞, 申竹芳, 等. 非酶糖基化终末产物与糖尿病肾脏并发症[J]. 中国临床药理学杂志, 2003,19(3):215-219.
46. George L, Hisao et al. Theoretical mechanisms by which hyperglycemia and insulin resistance could cause cardiovascular disease in diabetes[J]. Diabetes Care, 1999,22(Suppl):831-838.
47. Kelly J, Zhang Yuan, et al. Protein Kinase C [beta] inhibition atenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension[J], 2003,52(2):512-518.
48. Bryan W, Barbara G, et al. Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro[J]. Diabetes,1997,46:1497-1503.
49. Ruiz M, Lorenzo O, et al. Angiotensin II increases MCP-1 and activates Nfis B and AP-1 in cultured mesangial and mononuclear cell[J]. Kidney Int, 2000,57(6):2285-2298.
50. Seranian A, Shen L, et al. Inhibition of LDL, oxidation and oxidized LDL induced cytoxicity by dihydropyridine calcium antagonists[J]. Pharm Res, 2000,17(8):999-1008.
51. Suzuki S, Hinokio Y, et al. Oxidative damage of mitochondria DNA and its relationship to diabetic nephropathy[J]. Diabetes Res Clin Prac, 1999,45: 161-171.
52. Antonio Ceriello. New insights on oxidative stress and diabetic complication lead to a "causal" antioxidant theraphy[J]. Diabetes Care, 2003,26:1589-1597.
1. 王忠壮. 楤木属药用植物资源调查[J]. 中国中药杂志, 1997,22(1):3.
2. 江苏新医学院 中药大辞典[M]. 上海: 上海人民出版社, 1997,2583.
3. 崔树玉. 龙牙楤木化学成分研究[J]. 中成药, 1993,15(2):41.
4. SATOH YOHKO. Oleanolic acid saponins from root bark of Aralia[J]. phytochemistry, 1994,36(1):147.
5. Satoh Yohko, Shigant Sakai, Musami Katsumats. Oleanolic acid saponins from rootbark of aralia elata[J]. Phytochemistry, 1994,36(1):147.
6. Masayuki Yoshiknwa, Uisashi Maiauda, Limika Jlarada. Elatoside E: a new hypoglycemic primiple from the root cortex of a elata. Seem: structure-related hypoglycemic acid glycoside[J]. Chem Plarm Bull. 1994,42(6):1354.
7. 王忠壮, 胡晋红, 主编. 楤木属植物的生物学研究及应用. 上海: 第二军医大学出版社, 2001,102.
8. 西田奎志. 辽东楤木中皂甙对肝炎的效果[J]. 国外医学·中医中药分册. 1990,12(4):63.
9. 宋少江, 徐绥绪. 辽东楤木中的新化合物[J]. 中国药物化学杂志, 1999,42(5):125.
10. 孙晓波. 龙牙楤木的强壮作用[J]. 中草药, 1991,22(2):78.
11. 周重楚, 师海波, 李文亭, 等. 龙牙楤木的抗缺氧作用[J]. 中草药, 1991, 22(3):114.
12. 邓汉武. 辽东楤木总甙对大鼠实验性心肌缺血的保护作用[J]. 中国药理学与毒理学杂志, 1998,2(1):20.
13. 姜永涛. 辽东楤木的化学成分及药理活性研究[J]. 沈阳药学院学报, 1991,8(4):290.
14. 周重楚. 龙牙楤木总甙对变态反应的影响[J]. 中国药理学与毒理学杂志,1991,5(1):30.
15. 吉林省中医中药研究所. 长白山植物志[M]. 吉林: 吉林人民出版社, 1982,782.
16. 周重楚. 龙牙楤木总甙的抗炎作用[J]. 中国药理学与毒理学杂志, 1991,5(1):34.
17. 李 凡 . 龙 牙 楤 木 总 甙 的 抗 病 毒 作 用 研 究 [J]. 中 国 中 药 杂 志 , 1994,19(4):562.
18. 姜永涛. 辽东楤木化学成分研究[J]. 药学学报, 1992,27(7):528.
19. 龚希彬. 刺老芽毒性实验研究报告[J]. 中医药学报, 1989,2:56.
[1] WHO. Diabetes program, Http: //www.who.int/diabetes/cn.
[2] International Diabetes Federation. Diabetes Attlas [R]. Brussels [sn]. 2003.
[3] 刘钟梅, 李绥晶, 李欣, 等. 辽宁省成年居民糖尿病患病现状及其相关因素分析. 中国慢性病预防与控制. 2006,14(4):235-238.
[4] Rubler S, Dulgash J, Yuceoglu Y, et al. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972,30(6): 595-602.
[5] Hamy RI, Zoneraish S, Sherman L, et al. Diabetic cardiomyopathy [J]. JAMA, 1974,229(13):1749-1754.
[6] Nesto RW. Pharmacological treatment and prevention of heart failure in the diabetic patient. Rev Cardiovasc Med, 2004,5(1):1-8.
[7] Laetitia P, Jan M, Iris S, et al. Mechanisms of [Ca2+]: transient decrease in cardiomyopathy of db/db type 2 diabetic mice. Diabetes, 2006,55(3):608-615.
[8] Wang DW, Kiyosue J, Shigen atsu S, et al. Abnormalities of K+ and Ca2+ currents in ventricular myocytes from rats with chronic diabetes [J]. Am J Physiol. 1995,769:H1228-1296.
[9] Chatton S, Diacono J, Feuvray D. Decrease in sodium-calcium exchange and calcium current in diabetic rat ventricular myocytes [J]. Acta Physiol Scand, 1999,166:137-144.
[10] Russ M, Reinaue H, Eckel J. Diabetes-induced decrease in the mRNA coding for sarcoplasmic reticulum Ca2+-ATPase in adult rat cardiomyocytes [J]. Biochem Biophys Res Comm, 1991,178:906-912.
[11] Ziegelhoffer A, Ravingerova T, Styk J, et al. Diabetic cardiomyopathy in rats: biochemical mechanisms of increased tolerance to calcium everload. DiabetesRes Clin Pract, 1996,31:S93-103.
[12] Jen Z, Yu, Brian Rodrignes, John H. Intracellular calcium levels are uncharged in the diabetic heart. Cartiovasc Res. 1997,34(1):91-98.
[13] Miznshge K, Yao L, Noma J, et al. Alteration in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type II diabetic rat model. Circulation. 2000,101(8):899-907.
[14] Fredersdorh S, Thumann C, Ulucan C, et al. Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats. Cardiovasc Pathol, 2004,13(1):11-19.
[15] Way KJ, Isshiki K, Suzuma, et al. Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C beta 2 activation and diabetes. Diabetes, 2002,51(9):2709-2718.
[16] Dunca MR, Frazier KS, Abramson S, et al. Connective tissue growth factor mediates transforming growth factor beta induced collagen synthesis: down-regulation by camp FASEB. 1999,13:1774-1786.
[17] 王忠壮, 胡晋红, 主编. 楤木属植物的生物学研究及应用. 上海: 第二军医大学出版社, 2001,102.
[18] 赵春艳, 郭春尧, 张义, 等. 龙牙葱木皂苷对离体心脏的正性肌力作用. 吉林大学学报(医学版). 2002,28(3):244-246.
[19] 葛敬岩, 郭春尧, 赵春艳, 等. 龙芽葱木皂苷对大鼠血流动力学的影响. 白求恩医科大学学报, 2001,27(6):601-602.
[20] 周重楚. 龙芽楤木的抗缺氧作用[J]. 中草药, 1991,22(3):114.
[21] 刘建华, 常波. 辽东楤木对过度训练大鼠心肌线粒体游离钙的影响. 天津体育学院学报, 2006,21(5):423-425.
[22] Fein FS, kornstein LB, Strobecket TE, et al. Altered myocardial mechanics indiabetic rats. Cir Res, 1980,47:922-933.
[23] Yatan A, Bahinski A, Mikala G. single amino acid substitutions within the ion permeation pathway alter single-channel conductance of the human L-type cardiac Ca2+ channel. Circ Res. 1994,75:315-323.
[24] L. H. 奥佩, 高天祥译. 心脏生理学, 北京科学出版社. 2001,9.
[25] Golfman LS. Takeda N, Dhalla NS. Cardiac membrane Ca2+-transport in alloxan-induced diabetes in rats. Diabetes Res Clin Pract, 1996,31(suppl):s 73-77.
[26] Ligeti L, Szenczi O, Prestia CM, et al. Altered calcium handling in an early sign of streptozotocin-induced diabetic cardiomyopathy. Int Mol Med, 2006,17(6) 1035-1043.
[27] Chattou S, Diaconu J, Feuvray D, et al. Decreased in sodium-calcium exchange and calcium currents in diabetic rat ventricular myocyte [J]. Acta Physiol Scand, 1999,166(2):137-144.
[28] Yang JM, Choic H , Ikory KA, et al. Increased expression Galphag protein in the heart of streptocotocin-induced diabetes rats [J]. EXP Mol Med, 1999, 31(4):129-134.
[29] Zhao XY, Hu SJ, Li J, et al. Decreased cardiac. sarcoplasmic reticulum Ca2+-ATPase activity contributes to cardiac dysfunction in streptozotocin-induced diabetic rats. J Physiol Biochem. 2006,62(1)1-8.
[30] Hattori Y, Matsuda N, kimura J, et al. Diminished function and expression of cardiac Na+-Ca2+ exchanger in diabetic rats: implication in Ca2+ overload [J]. J Physiol, 2001,527:85-94.
[31] Shimon Y, Firek L severson D, et al short-term diabetes alters K+ current sin rat ventricular myocytes [J]. Cite Res, 1994,74:622-628.
[32] Dayi Qin, Boyu Huang, LiLi Deng, et al. Down regulation of K+ channelgenes expression in type I diabetic cardiomyopathy. Biochem & Biophys Res Comm. 2001,28(3):549-543.
[33] Cosis, O, Echevarria E. Diabetic cardiomyopathy electromechanical cellular alteration [J]. Curr Vas Pharmacol, 2004,2:237-248.
[34] 李勋, 杨向军, 蒋文平. 糖尿病大鼠心室肌细胞钾通道的改变[J]. 中华高血压杂志, 2006,14(8):647-650.
[35] Tahilini AG, Vadlamudl RVSV, Mc Nell AJH. Prevention and reversal of altered myocardial function in diabetic rats by insulin treatment. Can J Physiol Pharmacol, 1983, 61:516-523.
[36] Bertoluci MC, Schmid H, Lachat JJ, et al. Transforming growth factor-beta in the development of rat diabetic nephropathy. A 10-month study with insulin-treated rats [J]. Nephron, 1996,74(1):189-196.
[37] Frazier K, Williams, kothapalli D, et al. Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor. J Invest Dermatol, 1996,107(3):404-413.
[38] Leask A, Holmes A, Abraham DJ. Connective tissue growth factor: a new and important player in the pathogenesis of fibrosis. Curr Pheumatol Rep 2002,4:136-142.
[39] 邓汉武, 李元建, 沈乃, 等. 辽东楤木总甙对大鼠实验性心肌缺血的保护作用. 中国药理学与毒理学杂志, 1988,1.
[40] Ku DD, sellers BM. Effect of streptozotocin diabetes and insulin treatment on myocardial sodium pump and contractility of the rat heart [J]. J pharmacol EXP Ther, 1992,222:395-406.
[1] 叶任高, 陆再英, 主编. 内科学. 人民卫生出版社, 2004,2.
[2] Mogensen CE. Early Diabetic Renal Involvement and Nephropathy. In Albert KGMM krall. LP The Diabetes Annual vol3 Amsterdam , Elsevier Science Publishers, 1987,306.
[3] 于琳华, 任淑婷, 李恒力, 等. 早期糖尿病肾病的组织学及超微结构病变观察. 西安医科大学学报. 1999,20(4)504-506.
[4] Kreisbery L, Radmile RA, Ayosh J, etal. High glucose elevates c2fos and c2jun transcripts and proteins in mesangial matrix to elevated glucose reduce collagen synthesis and proteoglycan charge. Kidney Int. 1994,45:105.
[5] Banu V, Hara H, Okarnura M, etal. Urinary excretion of type IV collagen and laminin in the evalution of nephropathy in NIDDM: comparision with urinary albumin and markers of tubular disfunction and/or damage. Diabetes Res Clin Pract. 1995,29(1):57.
[6] Meyer L, Szukic B, Neubauer K, et al. Extracellular matrix proteins as early markers in diabetic nephropathy. Eur J Clin Cem Clin Biochem. 1995,33:211.
[7] Riser BL, Denichilo M, Cortesp, et al. Regulation of connective tissue growth factor activity in cultured rat mesangial cells and its expression in experimental diabetic glomerulosclerosis. J Am Soc Nephrol. 2000,11:25-28.
[8] 肖厚勤, 张建鄂, 丁国华, 等. 肾脏结构组织生长因子的检测及其对糖尿病肾病早期诊断的价值, 中国糖尿病杂志. 2006,14(1):37-40.
[9] Frazier K, Williams, Kothapalli D, et al. Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connectivetissue growth factor. J Invest Dematol, 1996,107(3):404-413.
[10] Yokoi H, Sugawara A, Mukoyama M, et al. Role of connective tissue growth factor in TGF-beta induced fibronectin expression in rat renal fibroblasts, and lts upregulation in obstructive nephropathy. J Am Soc Nephrol, 2000,11:540-548.
[11] Gupta S, Clarkson MR, Duggar J, et al. Connective tissue growth factor: potential role in glomerulosclerosis and tubulointerstitial fibrosis. Kidney Int, 2000,58(4):1389-1399.
[12] Tsilibary EC. Microvascular basement membranes in diabetes mellitus. J Pathol, 2003,200(4):537-46.
[13] Basile DP. The transforming growth factor beta system in kidney disease and repair : recent progress and future directions. Curr Opin Nephrol Hypertens, 1999,8(1):21-30.
[14] Lin BC, Chen O, Luo DD, et al. Mechanism of irbesartanin prevention of renal lesionin streptozotocin-induced diabetic rats. Acta Pharmacol Sin, 2001,276:16797-16803.
[15] Westen BS, Wahab NA, Mason RM, CTGF mediates TGF-beta-induced fibronectin matrix deposition by upregulating active alpha5 beta1 integrin inhuman mesangial cells [J]. J Am Soc Nephrol, 2003,14(3):601-610.
[16] Wahab NA, Yevdokimova N, Weston BS et al. Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy [J]. Biochem J. 2001,259(ptl):77-87.
[17] Yokoi H, Mukoyama M, Sugawara A, et al. Role of connective tissue growth factor in fibronectin expression and tubulo interstitial fibrosis [J]. Am J Physiol Renal Physiol, 2002,282(5):F933-942.
[18] Ito Y, Aten J, Bende RJ, et al. Expression of connective tissue growth factorin human renal fibrosis [J]. Kidney Int, 1998,53(4):853-861.
[19] Wang S, Denichil M, Brubaker C et al. Connective tissue growth factor in tubulointersititial injury of diabetic nephropathy [J]. Kidney Int. 2001,60(1):96-105.
[20] Sharma K, Ziyadeh FN. Renal hypertrophy is associated with upregulation of TGF-beta 1 gene expression in diabetic BB rat and NOD mouse [J]. Am J Physiol Renal Physiol, 1994,267(6):F1094-1100.
[21] Ziyadeh FN, Han DC. Involvement of transforming growth factor-beta and its receptors in the pathogenesis of diabetic nephrology [J]. Kidney Int Suppl, 1997,60:S7-11.
[22] 韩 晓 芳 , 潘 时 中 . 转 化 生 长 因 子 β 与 糖 尿 病 肾 病 . 医 学 综 述 . 2005,11(6):509-511.
[23] Basile DP. The transforming growth factor beta system in kidney disease and repair: recent progress and future directions. Curr Opin Nephrol Hypertens, 1999,8(1):21-30.
[24] Liu BC, Chen Q, Luo DD, et al. Mechanisms of irbesartan in prevention of renal lesion in streptozotocin-induced diabetic rats. Acta Pharmacol Sin, 2001,276:16797-16803.
[25] Core-Hyer E, Shegogue D, Markiewicz M, et al. TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal cells. Am J Physiol Renal Physiol, 2002,283:F707-716.
[26] Zhang C, Meng X, Zhu Z, et al. Role of connective tissue growth factor in renal tubular epithelial-myofibroblast transdifferentiation and extracellular matrix accumulation in Vitro. Life Sci, 2004,75:367-379.
[27] Abdel-Wahab N, Weston BS, Roberts T, et al. Connective tisssue growth factor and regulation of the mesangial cell cycle: role in cellular hypertrophy. J Am Soc Nephrol, 2002,13(10):2437-2445.
2. Hamby RI, Zoneraish S, Sherman L, et al. Diabetic cardiomyopathy[J]. JAMA 1974,229(13):1749-1754.
3. Ren J, Davidoff AJ. Diabetes rapidly induces contractile dysfunctions in isolated ventricular myocytes[J]. Am J Physiol, 1997,272:H140-158.
4. Davidoff AJ, Ren J, Low insulin and high glucose induce abnormal relaxation in cultured adult rat ventricular myocytes[J]. Am J Physiol, 1997,272: H159-167.
5. Okumura K, Akiyama N, Hashimoto H, et al. Alteration of 1,2-diacylglycerol content in myocardium from diabetic rats. Diabetes, 1998,37(9):1168-1172.
6. Way KJ, Katai N, King GL. Protein kinase C and the development of diabetic vascular complications. Diabet Med, 2001,18(12):945-959.
7. Way KJ, Isshiki K, Suzuma K, et al. Expression of connective tissue growth factor in increased in injured myocardium associated with protein kinase C beta 2 activation and diabetes. Diabetes, 2002,51(9):2709-2718.
8. Ramirez LC, Arauz Pacheco C, Lackner C, et al. Lipoprotein (a) levels in diabetes mellitus: relationship to metabolic control. Ann Interned 1992,117:42-47.
9. Mcneill JH. Role of elevated lipid in diabetic cardiomyopathy. Diabetes Res Clin Pract, 1996,31(suppl):S67-71.
10. Kennedy AL, Lyons TJ. Glycation, Oxidation, and Lipoxidation in the development of diabetic complication. Metabolism, 1997,46:14-21.
11. Shepherd, Ca MC, Sambandam N et al. Streptozotocin-induced diabetes enhances cardic heparin-releasable lipoprotein lipase activity in spontaneously hypertension rats[J]. Hypertension, 1998,31(8):878-884.
12. Oshima M, Higashi S, Autoradiographic study of myocardial fatty acid metebolism in diabetic mouse using 125I MPIPP[J]. Nipon Igaku Hoshasen Gakkai Zasshi, 1996,56(3):137-141.
13. Finck BN, Han X, Courtois M et al. A critical role for PPAR alpha-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: modulation by dietary fat content[J]. PNAS, 2003,100(3):1226-1231.
14. Dillmann WH. Diabetes and thyroid-hormore-induced changes in cardiac function and their molecular basis[J]. Annv Rev Med, 1989,40:373-394.
15. Hofmann PA, Menon V, Gennaway KF. Effects of diabetes on isometric tension as a function of [Ca2+] and PH in rat skinned cardiac myocytes[J]. Am J Physiol, 1995,2669:H1656-H1663.
16. Stanky WC, lopaschuk GD, Mc cormack JG. Regulation of energy substrate metabolism in the diabetic heart[J]. Cardiovasc Res, 1997,34:25-33.
17. Hsu K, Tsai L, Chiang CH, et al. Myocardial mechanics and titin in experimental insulin-resistant rats[J]. Jpn Heart, 1997,38:717-728.
18. Ligeti L, Szenczi O, Prestia CM, et al. Altered calcium handling is an early sign of streptozotocin-induced diabetic cardiomyopathy. Int Mol Med, 2006,17(6):1035-1043.
19. 心脏生理学. L.H. 奥佩著. 高天祥, 高天礼, 译. 北京: 科学出版社出版, 2001,9.
20. Perez PJ, dRamos-Franco J, Fill M, et al. Identificational and functional reconstitution of the type 2 1,4,5-trisphosphate receptor from vertricular cardiac myocytes, j Biol Chem, 1997,272:23961-23969.
21. Lompre A-M, Anger M, Levitsky D. Sarco (endo) plasmic reticulum calcium pumps in the cardiovascular system function and gene expression. J Mol Cell Cardiol, 1994,26:1109-1121.
22. Tada M, Katz Am. Phosphorylation of sarcoplasmic reticulum and sarcolemma. Annu Rev Physiol, 1982,44:401-423.
23. Hattori Y, Matsuda N, Kimura J, et al. Diminished function and expression of the cardiac Na+-Ca2+ exchanger in diabetic rats: implication in Ca2+ Overload[J]. J Physoiol, 2001,527:85-94.
24. Russ M, Reinaue H, Eckel J. Diabetes-induced decrease in the mRNA coding for sarcoplasmic reticulum Ca2+-ATPase in adult rat cardiomyocytes[J]. Biochem Biophys Res Comm, 1991,178:906-912.
25. Chattou S, Diacono J, Feuvray D. Decrease in Sodium-calcium exchange and calcium currents in diabetic rat ventricular myocytes[J]. Acta Physiol Scand, 1999,166:137-144.
26. Zhao XY, Hu SJ, Li J, et al. Decreased cardiac sarcoplasminc reticulum Ca2+-ATPase activity contributes to cardiac dysfunction in streptozotocin- induced diabetic rats. J Physiol Biochem. 2006,62(1):1-8.
27. Bidasec KR, Zhang Y, Shao CH, et al. Diabetes increases formation of advanced glycation end product on sarco (endo)plasmic Ca2+-ATPase Diabetes. 2004,53(2):463-473.
28. Schaffer SW, Ballard-croft C, Boerth S, et al. Mechanism underlying depressed Na+/Ca2+ excharger activity in the diabetic heart. Cardiovasc Res, 1997,34(1):129-136.
29. Wang DW, Kiyosue J, Shigen atsu S et a. Abnormalities of K+ and Ca2+ currents in ventricular myocytes from rats with chronic diabetes[J]. Am J Physiol, 1995,769:H1288-1296.
30. Shimoni Y, Firek L, Severson D, et al. Short-term diabetes alters K+ currents in rat Ventricular myocytes[J]. Cite Res, 1994,74:622-628.
31. Yang JM, Choic H, Ikorg KA, et al. Increased expression Galphaq protein in the heart of streptozotocin-induced diabetes rats [J]. Exp Mol Med, 1999,31(4):129-134.
32. Rodrigues B, Cam MC, MC Neill JH. Metabolic disturbances in diabetic cardiomyopathy[J]. Mol Cell Biochem, 1998,180:53-57.
33. Tanignchi N, Kaneto H, Asahi M, et al. Involvement of glycation and Oxidative stress in diabetic macroangiopathy. Diabetes, 1996,45(suppl,3): S81-83.
34. Nowri HO, Frei B, Keaney JF. Glucose enhancement of LDL oxidation is strictly metal iondependent. Free Radical Biol Med, 2000,29:814-824.
35. Kucharska J, Braunova Z, Ulcna O, et al. Dificit of coenzyme Q in heart and liver mitochondria of rats with streptozotocin-induced diabetes Physiol Res. 2000,49:411-418.
36. Brownlee M. Biochemistry and molecular cell biology of diabetic complication [J]. Nature, 2001,414(6865):813-820.
37. Cai L, Wang Y, Zhou G, et al. Attenuation by metallothionein of early cardiac death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy. J Am Coll Cardiol, 2006,48(8):1688-1697.
38. Vecchini A, Del Rosso F, Binaglia L, et al. Molecular defects in sarcolemmal glycerophospholipid subclasses in diabetic cardiomyopathy J, Mol Cell Cardiol, 2000,32:1061-1074.
39. Brown L, Wall D, Marchant C, et al. Tissue specific changes in angiotensin Ⅱreceptors in streptozotocin diabetic rats, J Endocronal, 1997,154:355.
40. Kim S, Wanibuchi H, Hamaguchi A, et al. Angiotensin blockade improvescardiac and renal complications of type II diabetic rats. Hypertension, 1997,30(5):1054-1061.
41. Fiordaliso F, Li B, Latini R, et al. Myocyte death in streptozotocin-induced diabetes in rats in angiotensin II-dependent [J]. Lab Invest, 2000,80:513-527.
42. Kajstura J, Fiordaliso F, Andreol: Am, et al. IGF-1 overpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress. Diabetes, 2001,50(6):1414-1424.
43. Fredersdorh S, Thumann C, Ulucan, C, et al. Myocardial hypertrophy and enhanced left ventricular contractility in zucker diabetic fatty rats Cardiovasc Pathol, 2004,13(1):11-19.
44. Feng Q, Lambert ML, Collow ID, et al. Venous neuropeptide Y receptor responsiveness in patients with chronic heart failure[J]. Clin Pharmacol Ther, 2000,67(3):292-298.
45. Millar BC, Plper HM, Mc Dermott BJ. The antiadrenergic effect of neuropeptide Y on the ventricular cardiomyocyte[J]. Naunyn Schmiedebergs Arch Pharmacol, 1998,338(4):426-429.
46. Mihtante JD, Lombardini JB, Shaffer SW. The role of tanrine in the pathogenesis of the cardiomyopathy of insulindependent diabetes mellitus[J]. Cardiovase Res, 2002,46(3):393-402.
47. 朱禧星, 周晓明, 何德华, 等. 链脲佐菌素糖尿病大鼠的心肌病变. 中华内分泌代谢杂志. 1992,8(4):222.
48. 周晓明, 钟学礼, 朱禧星, 等. 自发性遗传性糖尿病 BB 鼠慢性心脏超微结构病变的定量研究. 中华医学杂志, 1990,70(5):28-30.
49. Wijffels MC, Kirchhof CJ, Dorland R, et al. Atrial fibrillation begets atrial fibrillation Study in awake chronically instrumented goats. Circulation, 1995,92(7):1954-1968.
50. Aomine M, Nobe S, Arita M. Increased susceptibility to hypoxia prolonged action potential duration in ventricular papillary muscles from diabetic rats. Diabetes, 1990,39:1485-1489.
51. Casis D, Gallege M, Iriarte M, et al. effects of diabetic cardiomyopathy on regional electrophysiologic characteristics of rat ventricular [J]. Diabetologia, 2000,43(1):101-109.
52. Pacher D, Ungvari ZJ, Nanasi PP, et al. Electrophysiological changes in rat ventricular and atrial myocardium at different stage of experimental diabetes [J]. Acta Physiol Scard, 1999,166(1):7-13.
53. Lagadic-Grossmann D, Bucker KJ, Prigent KL, et al. Altered Ca2+ handling in ventricular myocytes isolated from diabetic rats [J]. Am J Physiol, 1996, 270(5):H1529-H1537.
54. Fein FS, Kornstein LB, Strobecket JE, et al. Altered myocardial mechanics in diabetic rats. Cir Res. 1980,47:922-933.
55. Zhong M, Zhang Y, Miao Y, et al. Mechanism of reversion of myocaodial interstitial fibrosis in diabetic cardiomyopathy by valsartan. Zhong Hua Yi Xue Za Zhi, 2006,86(4):232-236.
56. Airaksinen KEJ. Effects of isometric exercise and heart rate on left ventricular filling pattern assessed by Doppler. Echocardiography. 1989,226:245-249.
1. Bradham DM, Igarashi A, Potter RL, et al. Connective tissue growth factor: a cystein-rich mitogen secreated by human vascular endothelial cells is related to the SRC induced immediate early gene product CEP 10 [J]. J Cell Biol, 1991,114(6):1285-1294.
2. Frazier K, Williams, kothapalli D, et al. Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor. J Invest Dermatol, 1996,107(3):404-413.
3. Dickmeis T, plessy C, Rastegar S, et al. Expression profiling and comparative genomics identify a conserved regulatory region controlling midline expression in the zebrafish embro. Genome Res, 2004,14(2):228-238.
4. Lau LF, Lam SC. The CCN family of angiogenic regulators the intergin connection. Exp Cell Res, 1999,248(1):44-57.
5. Segarini PR, Nesbitt JE, Li D, et al. The low density lipoprotein receptor-related protein/alpha2-macroglobulin receptor is a receptor for connective tissue growth factor. I Biol Chem, 2001,276(44):40659-40667.
6. Nishida T, Nakanishi T, Shimo T, et al. Demonstration of reecptors specific for connective tissue growth factor on human chondrocytic cell line (HCS-2/8). Biochem Biophys Res Commun. 1998,247:905-916.
7. Wahab NA, Brinkman H, Mason RM, et al. Uptake and intracellular transport of the conneetive tissue growth factor: a potential mode of actin. Biochem J, 2001,359(pt1):89-97.
8. Yang M, Huang H, Li J, et al. Tyrosine phosphorylation of the LDL receptor-related protein (LRP) and activation of the EPK pathweay are required for connective tissue growth factor to potentiate myofibroblastdifferentiation, FASEB J, 2004,18(15):1920-1921.
9. Folger PA, Zekaria D, Grotendot G, et al. Transforming growth factor-beta-stimulated connective tissue growth factor expression during corneal myofibroblast differentiation. Invest Ophthal Mol Uis Sci, 2001,42(11):2534-2541.
10. Leask A, Holmes A, Abraham DJ. Connective tissue growth factor: a new and important player in the pathogenesis of fibrosis. Curr Pheumatol Rep 2002,4:136-142.
11. 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):213-219.
12. Chen Y, Abraham DJ, Xu shi-wen, et al. CCN2C (connective tissue growth factor) promotes fibroblast adhesion to fibronectin. Mol Biol Cell, 2004,15(12):5635-5646.
13. Chen CC, Chen N, Lan LT. The angiogenic factors Cyr61 and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts. J Biol Chem. 2001,276(13):10443-10451.
14. Shimo T, Nakanishi T, Kimura Y, et al. Inhibition of endogenous expression of connective tissue growth factor by its antisense ologonucleotide and antisense RNA suppresses proliferatin and migration of vascular endothelial cells. J Biochem Tokyo, 1998,124(1):130-136.
15. Abdel-Wahab N, Weston BS, Roberts T, et al. Connective tisssue growth factor and regulation of the mesangial cell cycle: role in cellular hypertrophy. J Am Soc Nephrol, 2002,13(10):2437-2445.
16. Cruzado JM, Ltoberas N, Torras J, et al. Regression of advanced diabetic nephropathy by hepatocyte growth factor gene therapy in rats. Diabetes,2004,53(4):1119-1127.
17. Riser BL, Denichilo M, Cortes P, et al. Regulation of connective tissue growth factor activity in cultured rat mesangial cells and its expression in experimental diabetic glomerulosclerosis. J Am Soc Nephrol, 2000,11:25-38.
18. McLennan SV, Wang XY, Moreno V, et al. Connective tissue growth factor mediates glucose effects of matrix degradation through tissue inhibitor of matrix metalloproteinase type I: implications for diabetic nephropathy. Endocrinology, 2004,145:5646-5655.
19. Kobayashi T, Inoue T, Okada H, et al. Connective tissue growth factor mediates the profibrotic effects of transforming growth factor-beta produced by tubular epithelial cells in response to high glucose. Clin Exp Nephrol, 2005,9:114-121.
20. Liu BC, Sun J, Chen Q, et al. Role of connective tissue growth factor in mediating hypertrophy of human proximal tubular cells induced by angiotensin II. Am J Nephrol, 2003,23:429-437.
21. Ruperez M, Ruiz-Ortega M, Esteban V, et al. Angiotensin II increases connective tissue growth factor in the kidney. Am J Pathd, 2003,163:1937-1947.
22. Ahmed MS, Qie E, Vinge LE, et a. Connective tissue growth factor-a novel mediator of angiotensin II-stimulated cardiac fibroblast activation in heart failure in rats. J Mol Cell Cardiol, 2004,36:393-404.
23. Zhou G, Li C, Cai L. Advanced glycation end-products induce connective tissue growth factor-mediated renal fibrosis predominantly through transforming growth factor beta-independent pathway. Am J Pathol, 2004,165:2033-2043.
24. Twigg SM, Joly AH, Chen MM, et al. Connective tissue growth factor/IGF-binding protein-related profein-2 is a mediator in the induction of fibronectin by advanced glycosylation end-products in human dermal fibroblasts. Endocrinology, 2002,143(4):1260-1269.
25. Duncan MR, Frazier KS, Abramson S, et al. Connective tissue growth factor mediates transforming growth factor beta induced collagen synthesis: down-regulation by camp. FASEB J. 1999,13:1774-1786.
26. Yokoi H, Sugawara A, Mukoyama M, et al. Role of connective tissue growth factor in TGF-beta induced fibronectin expression in rat renal fibroblasts and its upregulation in obstructive nephropathy. J Am Soc Nephrol, 2000,11:540-548.
27. Gupta S, Clarkson MR, Duggar J, et al. Connective tissue growth factor: potential role in glomerulosclerosis and tubulointerstitial fibrosis. Kidney Int, 2000,58(4):1389-1399.
28. Mori T, Kawara S, Shinozaki M, et al. Role and interaction of connective tissue growth factor with transforming growth factor beta in persistent fibrosis: A mouse fibrosis model. J Cell Physiol, 1999,18(1):153-161.
29. Hishikawa K, Oemar BS, Nakaki J, et al. Static pressure regulates connective tissue growth factor expression in human mesangial cells. J Biol Chem, 2001,276:16797-16803.
30. Liu BC, Chen Q, Luo DD, et al. Mechanisms of irbesartan in prevention of renal lesion in streptozotocin-induced diabetic rats. Acta Pharmacol Sin, 2001,276:16797-16803.
31. Lee CI, Guh JY, Chen HC, et al. Advanced glycation end-product-induecd mitogenesis and collagen production are dependent on angiotensin II and connective tissue growth factor in NRK-49F cell. J Cell Biochem, 2005,95:281-291.
32. Grothendorst GR, Rahmanie H, Duncan MR. Combinatorial signaling pathways determine fibroblast proliferation and myofibroblast differentiation. FASEB J, 2004,18:469-479.
33. Weston BS, Wahab NA, Mason RM. CTGF mediate TGF-beta induced fibronection matrix depositon by upregulating active alpha 5 beta1 integrin in human mesangial cells. J Am Soc Nephrol, 2003,14:601-610.
34. Core-Hyer E, Shegogue D, Markiewicz M, et al. TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal cells. Am J Physiol Renal Physiol, 2002,283:F707-716.
35. Lam S, Geest RN, Verhagen NA, et al. Connective tissue growth factor and IGF-1 are produced by human renal fibroblasts and cooperate in the induction of collagen production by high glucose. Diabetes, 2003,52:2975-2983.
36. Zhang C, Meng X, Zhu Z, et al. Role of connective tissue growth factor in renal tubular epithelial-myofibroblast transdifferentiation and extracellular matrix accumulation in Vitro. Life Sci, 2004,75:367-379.
37. Qi W, Twigg S, Chen X, et al. Integrated actions of transforming growth factor-betal and connective tissue growth in renal fibrosis. Am J Physiol Renal Physiol, 2005,288:F800-809.
38. Riser BL, Cortes P, DeNichilo M, et al. Urinary CCN2 (CTGF) as a possible predictor of diabetic nephropathy: preliminary report. Kidney Int, 2003,64:451-458.
39. Roestenberg P, Van Nienwenhoven FA, Wieten L, et al. Connective tissue growth factor is increased in plasma of type1 diabetic patient with nephropathy. Diabetes Care, 2004,27:1164-1170.
40. Nguyen TQ, Tarnow L, Andersen S, et al. Urinary Connective tissue growth factor excretion correlate with clinical markers of renal disease in a largepopulation of type I diabetic patient with diabetic nephropathy. Diabetes Care, 2006,29:83-88.
41. Candido R, Forbes JM, Thomas MC, et al. A breaker of advanced glycation end products attenuated diabetes-induced myocardial structural changes. Cir Res, 2003,1892(7):785-792.
42. Kerrie J, Keiji Isshiki, Kiyoshi suzuna, et al. Expression of connective tissue grwth factor is increased in injured myocardium associated with protein kinase C beta 2 activation and diabetes. Diabetes, 2002,51(9):2709-2718.
43. He Z, Way KJ, Arikawa E, et al. Differential regulation of angiotensin II-induced expression of connective tissue growth factor by protein kinase C isoforms in the myocardium. J Biol Chem. 2005,280(16):15719-19726.
44. 董志恒, 李才, 曲萌. 苯那普利对糖尿病大鼠心肌 CTGF 基因表达的影响及作用机制. 吉林大学学报 (医学版). 2004,30(4):520-523.
45. 赖鹏斌, 杨立勇, 林旭. 氟伐他汀对糖尿病大鼠心肌结缔组织生长因子表达的影响. 中国糖尿病杂志, 2006,14(3):224-226.
1. Hamby RI, Zoneraish S, Sherman L, et al. Diabetic cardiomyopathy [J]. TAMA 1974,229(13):1749-1754.
2. Lijian P, petrov V, Fagard R. Transforming growth factor-betal-mediated collagen gel concentration by cardiac fibroblasts [J]. J Renin Angiotensin Aldosterone Syst, 2003,4(2):113-138.
3. Laviades C, Varo N, Diez J. Transforming growth factorβ in hypertensives with cardiorenal damage [J]. Hypertension, 2000,36:517-522.
4. 孙卫民, 王惠琴. 细胞因子研究方法. 北京: 人民卫生出版社, 1999.
5. Mryazono K, Ichlio H, Heidin CH. Transforming growth factor-β, latent forms, binding proteins and receptors. Growth Factors, 1993,8(1):11-22.
6. Bottinger EP, Bitzer M. TGF-β signaling in renal disease [J]. J Am Soc Nephrol, 2002,13(10):2600-2610.
7. Choi ME. Mechanism of transforming growth factor-betal signaling [J]. Kidney Int Suppl, 2000,77:S53-58.
8. Yang H, Lu Y, Shen H. Influence of transfection of sense and antisense-TGF-betal gene on human pulmonary giant cell carcinoma cell proliferation. Zhong Hua Zhong Liu Za zhi, 1997,19:303-306.
9. Wieser R. The transforming growth factor-beta signaling pathway in tumorigenesis. Curr Opin Ocol, 2001,13(1):70-77.
10. Munger JS, Harpel JG, Gleizes PE, et al. Latent transforming growth factor-beta: structural features and mechanisms of activation. Kidney Int, 1997,51(5):1376-1382.
11. Blobe GC, Schiemann WP, Lodish HF. Role of transforming growth factor β in human disease. N Eng J Med, 2000,342:1350-1358.
12. Parving HH, Jacobser P. Rossing K, et al. Rossing benefits of long-term antihypertensive treatment on prognosis in diabetic Dephropathy. Kidney Int, 1996,49:1778-1782.
13. Massague J. Transforming growth factor-β family. Annu Rev Cell Biol, 1990,6:597-641.
14. Basile DP. The transforming growth factor beta system in kidney disease and repair: recent progress and future directions. Curr Opin Nephrol Hypertens, 1999,8(1):21-30.
15. Bertoluci MC, Schmid H, Lachat JJ, et al. Transforming growth factor-beta in the development of rat diabetic nephropathy. A 10-month study with insulin-treated rats [J]. Nephron, 1996,74(1):189-196.
16. Gambaro G, Ceol M, Del prete D, et al. GLUT-1 and TGF beta: the link between hyperglycaemia and diabetic nephropathy. Nephrol Dial Transplant, 2000,15(9):1476-1477.
17. Kagami S, Border WA, Miller DE, et al. Angiotensin II Stimulates extracellular matrix protein synthesis through induction of transforming growth factor-β expression in rat glomerular mesangial cells. J Clin Invest, 1994,93(6):2431-2437.
18. Campbell SE, Katwa LC. Angiotensin II stimulated expression of transforming growth factor beta-1 in cardiac fibroblasts and myofibroblasts. J Moll Cell Cardiol, 1997,29(7):1947-1958.
19. Mason RM, Wahab NA, Roger M, et al. Extracellular matrix metabolism in diabetic nephropathy [J]. J Am Soc Nephrol, 2003,14(5):1358-1373.
20. Iglesias-De La, Cruz MC, Ruiz-Torres P, et al. Hydrogen peroxide increases extracellular matric mRNA through TGF-β in human mesangial cells [J]. Kidney Int, 2001,59(1):87-95.
21. Chen S, Cohen MP, Ziyadeh FN. Amadori-glyacted albumin in diabetic nephropathy: pathophysiologic connections. Kidney Int, 2000,sep77:S40-44.
22. Kim YS, Kim BC, Song CY, et al. Advanced glycation end products stimulate collagen mRNA synthesis in mesangial cells mediated by protein kinase C and transforming growth factor-beta. J Lab Clin Med, 2001,138(1):59-68.
23. Guo M, Wu MH, Korompai F, et al. Upregulation of PKC gene and isozymes in cardiovascular tissues during early stages of experimental diabetes [J]. Physiol Genomics, 2003,12(2):139-146.
24. Cruden G, Zonca S, Hayward A, et a l. Mechanical stretch-induced fibronectin and transforming growth factor –β1 production in human mesangial cells is p38 mitogen-activated protein kinase-dependent [J]. Diabetes, 2000,49(5):655-661.
25. Everett AO, Mc Reddie AT, Fisher A, et al. Angiotensin receptor regulates cardic hypertrophy and transforming growth factor-beta1 expression [J]. Hypertension, 1994,23:587-592.
26. Brooks WW, Conrad CH. Myocardial fibrosis in transforming growth factor beta(1) heterozygous mice[J]. J Mol Cell Cardiol 2000,32(2):187-195.
27. Rerolle JP, Hertig A, Nguyen G, et al. plaminogen activator inhibitor type 1 is a potential target in renal fibrogenesis [J]. Kidney Int, 2004,58(5):1841-1850.
28. 范吴强. TGF-β1 和 Ang II 的相互作用在肾脏病中的意义. 国外医学·泌尿系统分册, 2000,20(5):536-540.
29. Sun Y, Zhang J, Zhang JQ, et al. Local angiotensin II and transforming growth factor β 1 in real fibrosis of rats [J]. Hypertension, 2000,35(5):1078-1084.
30. Li JP, Petrov V, Rumilla K, et al. Transforming growth factor betal promotes contraction of collagen gel by cardic fibroblasts through their differentiationinto myofibroblasts [J]. Methods Find EXP Clin Pharmacol, 2003,25 (2):79-86.
31. Sharma K, Ziyadeh FN. Renal hypertrophy is associated with upregulation of TGF-beta 1 gene expression in diabetic BB rat and NOD mouse [J]. Am J Physiol Renal Physiol, 1994,267(6):F1094-1100.
32. Wolf G, Ziyadeh FN. Molecular mechanisms of diabetic renal hypertrophy [J]. Kidney Int, 1999,56(2):393-405.
33. Ziyadeh FN, Han DC. Involvement of transforming growth factor-beta and its receptors in the pathogenesis of diabetic nephrology [J]. Kidney Int Suppl, 1997,60:S7-11.
34. Wolf G, Schanze A, Stahl, et al. p27 (kipl) knockout mice are protected from diabetic nephropathy: Evidence for p27 (kipl) haplotype insufficiency [J]. Kidney Int, 2005,68(4):1583-1591.
35. Akahori H, Ota T, Torita M, et al. Tranilast prevents the progression of experimental diabetic nephropathy through suppression of enhanced extracellular matrix gene expression [J]. J Pharmaco Ex Therap Therap, 2005,314(2):514-562.
36. McLennan SV, Fisher E, Martell SY, et al. Effects of glucose on matrix metalloproteinase aplasmin activities in mesangial cell: possible in diabetic nephropathy. Kidney Int, 2000,77(suppl):S81-87.
37. 韩 晓 芳 , 潘 时 中 . 转 化 生 长 因 子 β 与 糖 尿 病 肾 病 . 医 学 综 述 . 2005,11(6):509-511.
38. Iwano M, Quantification of glomerular TGF-β1 mRNA in patients with diabetes mellitus. Kidney Int, 1996,49(5):1120-1126.
39. Ina K, Kitanmura H, Tatsukawa S, et al. Transformation of intersititial fibroblasts and tubulointerstitial fibrosis in diabetic nephropathy [J]. MedElectron Microsc, 2002,35(2):87-96.
40. Li JH, Zhu HJ, Huang XR, et al. Smad7 inhibits fibrotic effect of TGF-beta on renal tubular epithelial cells by blocking Smad2 activation [J]. Jam Soc Nephrol, 2002,13(6):1464-1472.
41. Tsilibary EC. Microvascular basement membranes in diabetes mellitus. J Pathol, 2003,200(4):537-46.
42. Miyata T, Kurokawa K, et al. Relevance of oxidative and carbonyl stress to long-term uremic complications[J]. Kidney Int, 2000,58:120-125.
43. Angela G, Grit M, et al. Impact of metabolic control and serum lipids on the concentration of advanced glycation end products in the serum of children and adolescents with type 1 diabetes, as determined by fluorescence spectroscopy and N[epsilon]-(carboxymethyl) lysine ELISA[J]. Diabetes Care, 2003,26:2609-2621.
44. Copper ME, Gilbert RE, et al. Pathophysiology of diabetic nephropathy[J]. Metabolism, 1998,47 (Suppl): S3-S6.
45. 陈小瑞, 申竹芳, 等. 非酶糖基化终末产物与糖尿病肾脏并发症[J]. 中国临床药理学杂志, 2003,19(3):215-219.
46. George L, Hisao et al. Theoretical mechanisms by which hyperglycemia and insulin resistance could cause cardiovascular disease in diabetes[J]. Diabetes Care, 1999,22(Suppl):831-838.
47. Kelly J, Zhang Yuan, et al. Protein Kinase C [beta] inhibition atenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension[J], 2003,52(2):512-518.
48. Bryan W, Barbara G, et al. Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro[J]. Diabetes,1997,46:1497-1503.
49. Ruiz M, Lorenzo O, et al. Angiotensin II increases MCP-1 and activates Nfis B and AP-1 in cultured mesangial and mononuclear cell[J]. Kidney Int, 2000,57(6):2285-2298.
50. Seranian A, Shen L, et al. Inhibition of LDL, oxidation and oxidized LDL induced cytoxicity by dihydropyridine calcium antagonists[J]. Pharm Res, 2000,17(8):999-1008.
51. Suzuki S, Hinokio Y, et al. Oxidative damage of mitochondria DNA and its relationship to diabetic nephropathy[J]. Diabetes Res Clin Prac, 1999,45: 161-171.
52. Antonio Ceriello. New insights on oxidative stress and diabetic complication lead to a "causal" antioxidant theraphy[J]. Diabetes Care, 2003,26:1589-1597.
1. 王忠壮. 楤木属药用植物资源调查[J]. 中国中药杂志, 1997,22(1):3.
2. 江苏新医学院 中药大辞典[M]. 上海: 上海人民出版社, 1997,2583.
3. 崔树玉. 龙牙楤木化学成分研究[J]. 中成药, 1993,15(2):41.
4. SATOH YOHKO. Oleanolic acid saponins from root bark of Aralia[J]. phytochemistry, 1994,36(1):147.
5. Satoh Yohko, Shigant Sakai, Musami Katsumats. Oleanolic acid saponins from rootbark of aralia elata[J]. Phytochemistry, 1994,36(1):147.
6. Masayuki Yoshiknwa, Uisashi Maiauda, Limika Jlarada. Elatoside E: a new hypoglycemic primiple from the root cortex of a elata. Seem: structure-related hypoglycemic acid glycoside[J]. Chem Plarm Bull. 1994,42(6):1354.
7. 王忠壮, 胡晋红, 主编. 楤木属植物的生物学研究及应用. 上海: 第二军医大学出版社, 2001,102.
8. 西田奎志. 辽东楤木中皂甙对肝炎的效果[J]. 国外医学·中医中药分册. 1990,12(4):63.
9. 宋少江, 徐绥绪. 辽东楤木中的新化合物[J]. 中国药物化学杂志, 1999,42(5):125.
10. 孙晓波. 龙牙楤木的强壮作用[J]. 中草药, 1991,22(2):78.
11. 周重楚, 师海波, 李文亭, 等. 龙牙楤木的抗缺氧作用[J]. 中草药, 1991, 22(3):114.
12. 邓汉武. 辽东楤木总甙对大鼠实验性心肌缺血的保护作用[J]. 中国药理学与毒理学杂志, 1998,2(1):20.
13. 姜永涛. 辽东楤木的化学成分及药理活性研究[J]. 沈阳药学院学报, 1991,8(4):290.
14. 周重楚. 龙牙楤木总甙对变态反应的影响[J]. 中国药理学与毒理学杂志,1991,5(1):30.
15. 吉林省中医中药研究所. 长白山植物志[M]. 吉林: 吉林人民出版社, 1982,782.
16. 周重楚. 龙牙楤木总甙的抗炎作用[J]. 中国药理学与毒理学杂志, 1991,5(1):34.
17. 李 凡 . 龙 牙 楤 木 总 甙 的 抗 病 毒 作 用 研 究 [J]. 中 国 中 药 杂 志 , 1994,19(4):562.
18. 姜永涛. 辽东楤木化学成分研究[J]. 药学学报, 1992,27(7):528.
19. 龚希彬. 刺老芽毒性实验研究报告[J]. 中医药学报, 1989,2:56.
[1] WHO. Diabetes program, Http: //www.who.int/diabetes/cn.
[2] International Diabetes Federation. Diabetes Attlas [R]. Brussels [sn]. 2003.
[3] 刘钟梅, 李绥晶, 李欣, 等. 辽宁省成年居民糖尿病患病现状及其相关因素分析. 中国慢性病预防与控制. 2006,14(4):235-238.
[4] Rubler S, Dulgash J, Yuceoglu Y, et al. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972,30(6): 595-602.
[5] Hamy RI, Zoneraish S, Sherman L, et al. Diabetic cardiomyopathy [J]. JAMA, 1974,229(13):1749-1754.
[6] Nesto RW. Pharmacological treatment and prevention of heart failure in the diabetic patient. Rev Cardiovasc Med, 2004,5(1):1-8.
[7] Laetitia P, Jan M, Iris S, et al. Mechanisms of [Ca2+]: transient decrease in cardiomyopathy of db/db type 2 diabetic mice. Diabetes, 2006,55(3):608-615.
[8] Wang DW, Kiyosue J, Shigen atsu S, et al. Abnormalities of K+ and Ca2+ currents in ventricular myocytes from rats with chronic diabetes [J]. Am J Physiol. 1995,769:H1228-1296.
[9] Chatton S, Diacono J, Feuvray D. Decrease in sodium-calcium exchange and calcium current in diabetic rat ventricular myocytes [J]. Acta Physiol Scand, 1999,166:137-144.
[10] Russ M, Reinaue H, Eckel J. Diabetes-induced decrease in the mRNA coding for sarcoplasmic reticulum Ca2+-ATPase in adult rat cardiomyocytes [J]. Biochem Biophys Res Comm, 1991,178:906-912.
[11] Ziegelhoffer A, Ravingerova T, Styk J, et al. Diabetic cardiomyopathy in rats: biochemical mechanisms of increased tolerance to calcium everload. DiabetesRes Clin Pract, 1996,31:S93-103.
[12] Jen Z, Yu, Brian Rodrignes, John H. Intracellular calcium levels are uncharged in the diabetic heart. Cartiovasc Res. 1997,34(1):91-98.
[13] Miznshge K, Yao L, Noma J, et al. Alteration in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type II diabetic rat model. Circulation. 2000,101(8):899-907.
[14] Fredersdorh S, Thumann C, Ulucan C, et al. Myocardial hypertrophy and enhanced left ventricular contractility in Zucker diabetic fatty rats. Cardiovasc Pathol, 2004,13(1):11-19.
[15] Way KJ, Isshiki K, Suzuma, et al. Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C beta 2 activation and diabetes. Diabetes, 2002,51(9):2709-2718.
[16] Dunca MR, Frazier KS, Abramson S, et al. Connective tissue growth factor mediates transforming growth factor beta induced collagen synthesis: down-regulation by camp FASEB. 1999,13:1774-1786.
[17] 王忠壮, 胡晋红, 主编. 楤木属植物的生物学研究及应用. 上海: 第二军医大学出版社, 2001,102.
[18] 赵春艳, 郭春尧, 张义, 等. 龙牙葱木皂苷对离体心脏的正性肌力作用. 吉林大学学报(医学版). 2002,28(3):244-246.
[19] 葛敬岩, 郭春尧, 赵春艳, 等. 龙芽葱木皂苷对大鼠血流动力学的影响. 白求恩医科大学学报, 2001,27(6):601-602.
[20] 周重楚. 龙芽楤木的抗缺氧作用[J]. 中草药, 1991,22(3):114.
[21] 刘建华, 常波. 辽东楤木对过度训练大鼠心肌线粒体游离钙的影响. 天津体育学院学报, 2006,21(5):423-425.
[22] Fein FS, kornstein LB, Strobecket TE, et al. Altered myocardial mechanics indiabetic rats. Cir Res, 1980,47:922-933.
[23] Yatan A, Bahinski A, Mikala G. single amino acid substitutions within the ion permeation pathway alter single-channel conductance of the human L-type cardiac Ca2+ channel. Circ Res. 1994,75:315-323.
[24] L. H. 奥佩, 高天祥译. 心脏生理学, 北京科学出版社. 2001,9.
[25] Golfman LS. Takeda N, Dhalla NS. Cardiac membrane Ca2+-transport in alloxan-induced diabetes in rats. Diabetes Res Clin Pract, 1996,31(suppl):s 73-77.
[26] Ligeti L, Szenczi O, Prestia CM, et al. Altered calcium handling in an early sign of streptozotocin-induced diabetic cardiomyopathy. Int Mol Med, 2006,17(6) 1035-1043.
[27] Chattou S, Diaconu J, Feuvray D, et al. Decreased in sodium-calcium exchange and calcium currents in diabetic rat ventricular myocyte [J]. Acta Physiol Scand, 1999,166(2):137-144.
[28] Yang JM, Choic H , Ikory KA, et al. Increased expression Galphag protein in the heart of streptocotocin-induced diabetes rats [J]. EXP Mol Med, 1999, 31(4):129-134.
[29] Zhao XY, Hu SJ, Li J, et al. Decreased cardiac. sarcoplasmic reticulum Ca2+-ATPase activity contributes to cardiac dysfunction in streptozotocin-induced diabetic rats. J Physiol Biochem. 2006,62(1)1-8.
[30] Hattori Y, Matsuda N, kimura J, et al. Diminished function and expression of cardiac Na+-Ca2+ exchanger in diabetic rats: implication in Ca2+ overload [J]. J Physiol, 2001,527:85-94.
[31] Shimon Y, Firek L severson D, et al short-term diabetes alters K+ current sin rat ventricular myocytes [J]. Cite Res, 1994,74:622-628.
[32] Dayi Qin, Boyu Huang, LiLi Deng, et al. Down regulation of K+ channelgenes expression in type I diabetic cardiomyopathy. Biochem & Biophys Res Comm. 2001,28(3):549-543.
[33] Cosis, O, Echevarria E. Diabetic cardiomyopathy electromechanical cellular alteration [J]. Curr Vas Pharmacol, 2004,2:237-248.
[34] 李勋, 杨向军, 蒋文平. 糖尿病大鼠心室肌细胞钾通道的改变[J]. 中华高血压杂志, 2006,14(8):647-650.
[35] Tahilini AG, Vadlamudl RVSV, Mc Nell AJH. Prevention and reversal of altered myocardial function in diabetic rats by insulin treatment. Can J Physiol Pharmacol, 1983, 61:516-523.
[36] Bertoluci MC, Schmid H, Lachat JJ, et al. Transforming growth factor-beta in the development of rat diabetic nephropathy. A 10-month study with insulin-treated rats [J]. Nephron, 1996,74(1):189-196.
[37] Frazier K, Williams, kothapalli D, et al. Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connective tissue growth factor. J Invest Dermatol, 1996,107(3):404-413.
[38] Leask A, Holmes A, Abraham DJ. Connective tissue growth factor: a new and important player in the pathogenesis of fibrosis. Curr Pheumatol Rep 2002,4:136-142.
[39] 邓汉武, 李元建, 沈乃, 等. 辽东楤木总甙对大鼠实验性心肌缺血的保护作用. 中国药理学与毒理学杂志, 1988,1.
[40] Ku DD, sellers BM. Effect of streptozotocin diabetes and insulin treatment on myocardial sodium pump and contractility of the rat heart [J]. J pharmacol EXP Ther, 1992,222:395-406.
[1] 叶任高, 陆再英, 主编. 内科学. 人民卫生出版社, 2004,2.
[2] Mogensen CE. Early Diabetic Renal Involvement and Nephropathy. In Albert KGMM krall. LP The Diabetes Annual vol3 Amsterdam , Elsevier Science Publishers, 1987,306.
[3] 于琳华, 任淑婷, 李恒力, 等. 早期糖尿病肾病的组织学及超微结构病变观察. 西安医科大学学报. 1999,20(4)504-506.
[4] Kreisbery L, Radmile RA, Ayosh J, etal. High glucose elevates c2fos and c2jun transcripts and proteins in mesangial matrix to elevated glucose reduce collagen synthesis and proteoglycan charge. Kidney Int. 1994,45:105.
[5] Banu V, Hara H, Okarnura M, etal. Urinary excretion of type IV collagen and laminin in the evalution of nephropathy in NIDDM: comparision with urinary albumin and markers of tubular disfunction and/or damage. Diabetes Res Clin Pract. 1995,29(1):57.
[6] Meyer L, Szukic B, Neubauer K, et al. Extracellular matrix proteins as early markers in diabetic nephropathy. Eur J Clin Cem Clin Biochem. 1995,33:211.
[7] Riser BL, Denichilo M, Cortesp, et al. Regulation of connective tissue growth factor activity in cultured rat mesangial cells and its expression in experimental diabetic glomerulosclerosis. J Am Soc Nephrol. 2000,11:25-28.
[8] 肖厚勤, 张建鄂, 丁国华, 等. 肾脏结构组织生长因子的检测及其对糖尿病肾病早期诊断的价值, 中国糖尿病杂志. 2006,14(1):37-40.
[9] Frazier K, Williams, Kothapalli D, et al. Stimulation of fibroblast cell growth, matrix production, and granulation tissue formation by connectivetissue growth factor. J Invest Dematol, 1996,107(3):404-413.
[10] Yokoi H, Sugawara A, Mukoyama M, et al. Role of connective tissue growth factor in TGF-beta induced fibronectin expression in rat renal fibroblasts, and lts upregulation in obstructive nephropathy. J Am Soc Nephrol, 2000,11:540-548.
[11] Gupta S, Clarkson MR, Duggar J, et al. Connective tissue growth factor: potential role in glomerulosclerosis and tubulointerstitial fibrosis. Kidney Int, 2000,58(4):1389-1399.
[12] Tsilibary EC. Microvascular basement membranes in diabetes mellitus. J Pathol, 2003,200(4):537-46.
[13] Basile DP. The transforming growth factor beta system in kidney disease and repair : recent progress and future directions. Curr Opin Nephrol Hypertens, 1999,8(1):21-30.
[14] Lin BC, Chen O, Luo DD, et al. Mechanism of irbesartanin prevention of renal lesionin streptozotocin-induced diabetic rats. Acta Pharmacol Sin, 2001,276:16797-16803.
[15] Westen BS, Wahab NA, Mason RM, CTGF mediates TGF-beta-induced fibronectin matrix deposition by upregulating active alpha5 beta1 integrin inhuman mesangial cells [J]. J Am Soc Nephrol, 2003,14(3):601-610.
[16] Wahab NA, Yevdokimova N, Weston BS et al. Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy [J]. Biochem J. 2001,259(ptl):77-87.
[17] Yokoi H, Mukoyama M, Sugawara A, et al. Role of connective tissue growth factor in fibronectin expression and tubulo interstitial fibrosis [J]. Am J Physiol Renal Physiol, 2002,282(5):F933-942.
[18] Ito Y, Aten J, Bende RJ, et al. Expression of connective tissue growth factorin human renal fibrosis [J]. Kidney Int, 1998,53(4):853-861.
[19] Wang S, Denichil M, Brubaker C et al. Connective tissue growth factor in tubulointersititial injury of diabetic nephropathy [J]. Kidney Int. 2001,60(1):96-105.
[20] Sharma K, Ziyadeh FN. Renal hypertrophy is associated with upregulation of TGF-beta 1 gene expression in diabetic BB rat and NOD mouse [J]. Am J Physiol Renal Physiol, 1994,267(6):F1094-1100.
[21] Ziyadeh FN, Han DC. Involvement of transforming growth factor-beta and its receptors in the pathogenesis of diabetic nephrology [J]. Kidney Int Suppl, 1997,60:S7-11.
[22] 韩 晓 芳 , 潘 时 中 . 转 化 生 长 因 子 β 与 糖 尿 病 肾 病 . 医 学 综 述 . 2005,11(6):509-511.
[23] Basile DP. The transforming growth factor beta system in kidney disease and repair: recent progress and future directions. Curr Opin Nephrol Hypertens, 1999,8(1):21-30.
[24] Liu BC, Chen Q, Luo DD, et al. Mechanisms of irbesartan in prevention of renal lesion in streptozotocin-induced diabetic rats. Acta Pharmacol Sin, 2001,276:16797-16803.
[25] Core-Hyer E, Shegogue D, Markiewicz M, et al. TGF-beta and CTGF have overlapping and distinct fibrogenic effects on human renal cells. Am J Physiol Renal Physiol, 2002,283:F707-716.
[26] Zhang C, Meng X, Zhu Z, et al. Role of connective tissue growth factor in renal tubular epithelial-myofibroblast transdifferentiation and extracellular matrix accumulation in Vitro. Life Sci, 2004,75:367-379.
[27] Abdel-Wahab N, Weston BS, Roberts T, et al. Connective tisssue growth factor and regulation of the mesangial cell cycle: role in cellular hypertrophy. J Am Soc Nephrol, 2002,13(10):2437-2445.