肾血宁煎剂对原发性IgA肾病大鼠肾组织Ⅳ型胶原影响的实验研究
|
摘要
目的:
通过肾血宁煎剂对原发性IgA肾病大鼠肾组织Ⅳ型胶原表达的影响,探讨其对原发性IgA肾病肾纤维化的影响及作用机理,寻求延缓或阻止IgA肾病病程发展的有效药物。
方法:
体重160±20g的健康雌性Wistar大鼠48只,实验前,均做尿蛋白、尿潜血检查,排除非健康实验动物对实验结果的影响。随机分为4组,即空白对照组、模型组、肾血宁煎剂组、代文(缬沙坦)组,每组12只。随机选取3组,建立IgA肾病模型。12周后,观察大鼠24h尿蛋白定量、尿红细胞计数、血清肌酐、血尿素氮、肾组织形态学和Ⅳ型胶原表达等指标。
结果:
1、模型组大鼠24h尿蛋白定量明显升高(P<0.05),肾血宁煎剂组、代文(缬沙坦)组大鼠24h尿蛋白定量增高的幅度显著低于模型组(P<0.05),肾血宁煎剂组与代文(缬沙坦)组相比,无显著性统计学意义(P>0.05)。
2、模型组大鼠尿红细胞计数明显升高(P<0.05),肾血宁煎剂组大鼠尿红细胞计数增高的幅度显著低于模型组、代文(缬沙坦)组(P<0.05),代文(缬沙坦)组与模型组相比,无显著性统计学意义(P>0.05)。
3、模型组大鼠血清肌酐、血尿素氮明显升高(P<0.05),肾血宁煎剂组、代文(缬沙坦)组大鼠血清肌酐、血尿素氮增高的幅度显著低于模型组(P<0.05),肾血宁煎剂组与代文(缬沙坦)组相比,无显著性统计学意义(P>0.05)。
4、图像分析:模型组大鼠肾组织Ⅳ型胶原(Col一Ⅳ)平均光密度值明显升高(P<0.05),肾血宁煎剂组、代文(缬沙坦)组大鼠肾组织Ⅳ型胶原(Col一Ⅳ)平均光密度值增高的幅度显著低于模型组(P<0.05),肾血宁煎剂组与代文(缬沙坦)组相比,无显著性统计学意义(P>0.05)。
5、病理:
⑴HE染色结果:模型组大鼠肾小球明显肥大,肾小球系膜细胞增生伴系膜基质增多,部分肾小球节段性硬化,球囊壁粘连,肾小管上皮细胞空泡变性、肥大、增生,部分肾小管萎缩,肾间质有不同程度的单个核炎症细胞浸润和纤维化,肾血宁煎剂组、代文(缬沙坦)组大鼠较模型组程度明显减轻,且肾血宁煎剂组较代文(缬沙坦)组程度轻。
⑵免疫荧光结果:模型组、肾血宁煎剂组、代文(缬沙坦)组大鼠肾小球基底膜和系膜区均有亮绿色阳性染色沉积,肾血宁煎剂组、代文(缬沙坦)组的亮绿色阳性染色沉积较模型组少,肾血宁煎剂组的亮绿色阳性染色沉积较代文(缬沙坦)组少。
⑶免疫组化染色结果:空白对照组肾组织中Ⅳ型胶原(Col一Ⅳ)在肾小球毛细血管基底膜和系膜区、肾小管上皮细胞基底膜轻度表达,阳性染色为棕黄色颗粒,模型组中肾小球毛细血管基底膜和系膜区、肾小管上皮细胞基底膜及间质可见大量棕黄色颗粒沉积,肾血宁煎剂组、代文(缬沙坦)组棕黄色颗粒沉积较模型组明显减少,且肾血宁煎剂组较代文(缬沙坦)组程度轻。
结论:
1.肾血宁煎剂有降低原发性IgA肾病大鼠24小时尿蛋白、尿红细胞、血清肌酐、血尿素氮的作用。
2.肾血宁煎剂有降低原发性IgA肾病大鼠Ⅳ型胶原表达的作用。
3.肾血宁煎剂具有延缓IgA肾病病程发展的作用。其机制可能是通过降低Ⅳ型胶原表达,减轻ECM的过度蓄积,减轻了肾小球硬化和肾小管-间质纤维化,从而减轻尿蛋白、血尿,保护了肾功能。
Goal:
Through Shenxuening Jianji to primary IgA nephrosis big mouse's kidney organization in typeⅣCollagen expression influence, discusses it to the primary IgA nephrosis kidney fibrosis influence and the action mechanism, seeks the effective medicine to postpone or prevent the IgA nephrosis course development.
Method:
Body weight 160±20g healthy female Wistar big mouse 48, before the experiment, makes the urine protein, the urine occult blood inspection, removes the non-health experimental animal to the experimental result influence. Divides into 4 groups stochastically, namely blank control group, model group, Shenxuening Jianji group, Diovan (Valsartan) group, each group of 12. Selects 3 groups stochastically, establishes the IgA nephrosis model. 12 weeks later, observes the indicators about the big mouse 24h urine protein quota, the urine red cell count, the serum creatinine, the blood urea nitrogen, Renal morphology and expression of typeⅣcollagen ,and so on.
Finally:
1、The model group big mouse 24h urine protein quota is significantly increased (P <0.05),the rate of increase of the Shenxuening Jianji group、the Diovan (valsartan) group 24h urine protein quota levels is significantly lower than the rate of the model group (P <0.05),Compared the Shenxuening Jianji group with the Diovan (valsartan) group, there is no statistically significant (P> 0.05).
2、The model group big mouse urine red cell count is significantly increased (P <0.05),the rate of increase of the Shenxuening Jianji group urine red cell count levels is significantly lower than the rate of the model group、the Diovan (valsartan) group (P <0.05),Compared the Diovan (valsartan) group with the model group, there is no statistically significant (P> 0.05).
3、The model group big mouse serum creatinine、blood urea nitrogen is significantly increased (P <0.05),the rate of increase of the Shenxuening Jianji group、the Diovan (valsartan) group serum creatinine, blood urea nitrogen levels is significantly lower than the rate of the model group (P <0.05),Compared the Shenxuening Jianji group with the Diovan (valsartan) group, there is no statistically significant (P> 0.05).
4、Image Analysis:The model group big mouse kidney organization typeⅣCollagen(Col一Ⅳ)average optical density value is significantly increased (P <0.05),the rate of increase of the Shenxuening Jianji group、the Diovan (valsartan) group kidney organization typeⅣCollagen(Col一Ⅳ)average optical density value levels is significantly lower than the rate of the model group (P <0.05),Compared the Shenxuening Jianji group with the Diovan (valsartan) group, there is no statistically significant (P> 0.05).
5、Pathology:
⑴HE staining results: The model group big mouse glomerular is obviously hypertrophy, glomerular mesangial cells hyperplasia with Mesangial matrix increase, Part of glomerular Segmental sclerosis, ball wall adhesion, Renal tubular epithelial cells degeneration, hypertrophy, hyperplasia, Some tubular atrophy, Renal interstitial have varying degrees of mononuclear inflammatory cell infiltration and fibrosis, the Shenxuening Jianji group、the Diovan (valsartan) group compared to the model group is reduced significantly, and the Shenxuening Jianji group than the Diovan (valsartan) group level light.
⑵Immunofluorescence Results: The model group, Shenxuening Jianji group, the Diovan (Valsartan) group big mouse glomerular basement membrane and mesangial area have bright green positive staining deposition, Shenxuening Jianji group, the Diovan (Valsartan) group bright green positive staining deposition less than the model group, and Shenxuening Jianji group bright green positive staining deposition less than the Diovan (Valsartan) group.
⑶Immunohistochemical staining results: In the blank control group kidney organization ,typeⅣCollagen(Col一Ⅳ)has the Mild expression in the glomerular basement membrane and mesangial area, the basement membrane proximal tubular epithelial cells, positive staining for the brown granules ,and in the model group, glomerular basement membrane and mesangial area,renal tubular epithelial cells and the basement membrane mesenchymal show a large number of brown particle deposition. Shenxuening Jianji group, the Diovan (Valsartan) group brown granules deposition is significantly reduced compared to the model group,and Shenxuening Jianji group than the Diovan (Valsartan) group level light.
Conclusion:
1、The Shenxuening Jianji has the function of reducing the IgA nephrosis big mouse 24-hour urine protein and red blood cells, serum creatinine, blood urea nitrogen.
2、The Shenxuening Jianji has the function of reducing the primary IgA nephrosis big mouse expression of typeⅣcollagen.
3、The Shenxuening Jianji has the function of delaying the IgA nephrosis course development. Its mechanism may be by reducing expression of typeⅣcollagen,to reduce the excessive accumulation of ECM, reduce glomerulosclerosis and tubular - interstitial fibrosis, thereby reduce urine protein、hematuria, and Protect renal function.
通过肾血宁煎剂对原发性IgA肾病大鼠肾组织Ⅳ型胶原表达的影响,探讨其对原发性IgA肾病肾纤维化的影响及作用机理,寻求延缓或阻止IgA肾病病程发展的有效药物。
方法:
体重160±20g的健康雌性Wistar大鼠48只,实验前,均做尿蛋白、尿潜血检查,排除非健康实验动物对实验结果的影响。随机分为4组,即空白对照组、模型组、肾血宁煎剂组、代文(缬沙坦)组,每组12只。随机选取3组,建立IgA肾病模型。12周后,观察大鼠24h尿蛋白定量、尿红细胞计数、血清肌酐、血尿素氮、肾组织形态学和Ⅳ型胶原表达等指标。
结果:
1、模型组大鼠24h尿蛋白定量明显升高(P<0.05),肾血宁煎剂组、代文(缬沙坦)组大鼠24h尿蛋白定量增高的幅度显著低于模型组(P<0.05),肾血宁煎剂组与代文(缬沙坦)组相比,无显著性统计学意义(P>0.05)。
2、模型组大鼠尿红细胞计数明显升高(P<0.05),肾血宁煎剂组大鼠尿红细胞计数增高的幅度显著低于模型组、代文(缬沙坦)组(P<0.05),代文(缬沙坦)组与模型组相比,无显著性统计学意义(P>0.05)。
3、模型组大鼠血清肌酐、血尿素氮明显升高(P<0.05),肾血宁煎剂组、代文(缬沙坦)组大鼠血清肌酐、血尿素氮增高的幅度显著低于模型组(P<0.05),肾血宁煎剂组与代文(缬沙坦)组相比,无显著性统计学意义(P>0.05)。
4、图像分析:模型组大鼠肾组织Ⅳ型胶原(Col一Ⅳ)平均光密度值明显升高(P<0.05),肾血宁煎剂组、代文(缬沙坦)组大鼠肾组织Ⅳ型胶原(Col一Ⅳ)平均光密度值增高的幅度显著低于模型组(P<0.05),肾血宁煎剂组与代文(缬沙坦)组相比,无显著性统计学意义(P>0.05)。
5、病理:
⑴HE染色结果:模型组大鼠肾小球明显肥大,肾小球系膜细胞增生伴系膜基质增多,部分肾小球节段性硬化,球囊壁粘连,肾小管上皮细胞空泡变性、肥大、增生,部分肾小管萎缩,肾间质有不同程度的单个核炎症细胞浸润和纤维化,肾血宁煎剂组、代文(缬沙坦)组大鼠较模型组程度明显减轻,且肾血宁煎剂组较代文(缬沙坦)组程度轻。
⑵免疫荧光结果:模型组、肾血宁煎剂组、代文(缬沙坦)组大鼠肾小球基底膜和系膜区均有亮绿色阳性染色沉积,肾血宁煎剂组、代文(缬沙坦)组的亮绿色阳性染色沉积较模型组少,肾血宁煎剂组的亮绿色阳性染色沉积较代文(缬沙坦)组少。
⑶免疫组化染色结果:空白对照组肾组织中Ⅳ型胶原(Col一Ⅳ)在肾小球毛细血管基底膜和系膜区、肾小管上皮细胞基底膜轻度表达,阳性染色为棕黄色颗粒,模型组中肾小球毛细血管基底膜和系膜区、肾小管上皮细胞基底膜及间质可见大量棕黄色颗粒沉积,肾血宁煎剂组、代文(缬沙坦)组棕黄色颗粒沉积较模型组明显减少,且肾血宁煎剂组较代文(缬沙坦)组程度轻。
结论:
1.肾血宁煎剂有降低原发性IgA肾病大鼠24小时尿蛋白、尿红细胞、血清肌酐、血尿素氮的作用。
2.肾血宁煎剂有降低原发性IgA肾病大鼠Ⅳ型胶原表达的作用。
3.肾血宁煎剂具有延缓IgA肾病病程发展的作用。其机制可能是通过降低Ⅳ型胶原表达,减轻ECM的过度蓄积,减轻了肾小球硬化和肾小管-间质纤维化,从而减轻尿蛋白、血尿,保护了肾功能。
Goal:
Through Shenxuening Jianji to primary IgA nephrosis big mouse's kidney organization in typeⅣCollagen expression influence, discusses it to the primary IgA nephrosis kidney fibrosis influence and the action mechanism, seeks the effective medicine to postpone or prevent the IgA nephrosis course development.
Method:
Body weight 160±20g healthy female Wistar big mouse 48, before the experiment, makes the urine protein, the urine occult blood inspection, removes the non-health experimental animal to the experimental result influence. Divides into 4 groups stochastically, namely blank control group, model group, Shenxuening Jianji group, Diovan (Valsartan) group, each group of 12. Selects 3 groups stochastically, establishes the IgA nephrosis model. 12 weeks later, observes the indicators about the big mouse 24h urine protein quota, the urine red cell count, the serum creatinine, the blood urea nitrogen, Renal morphology and expression of typeⅣcollagen ,and so on.
Finally:
1、The model group big mouse 24h urine protein quota is significantly increased (P <0.05),the rate of increase of the Shenxuening Jianji group、the Diovan (valsartan) group 24h urine protein quota levels is significantly lower than the rate of the model group (P <0.05),Compared the Shenxuening Jianji group with the Diovan (valsartan) group, there is no statistically significant (P> 0.05).
2、The model group big mouse urine red cell count is significantly increased (P <0.05),the rate of increase of the Shenxuening Jianji group urine red cell count levels is significantly lower than the rate of the model group、the Diovan (valsartan) group (P <0.05),Compared the Diovan (valsartan) group with the model group, there is no statistically significant (P> 0.05).
3、The model group big mouse serum creatinine、blood urea nitrogen is significantly increased (P <0.05),the rate of increase of the Shenxuening Jianji group、the Diovan (valsartan) group serum creatinine, blood urea nitrogen levels is significantly lower than the rate of the model group (P <0.05),Compared the Shenxuening Jianji group with the Diovan (valsartan) group, there is no statistically significant (P> 0.05).
4、Image Analysis:The model group big mouse kidney organization typeⅣCollagen(Col一Ⅳ)average optical density value is significantly increased (P <0.05),the rate of increase of the Shenxuening Jianji group、the Diovan (valsartan) group kidney organization typeⅣCollagen(Col一Ⅳ)average optical density value levels is significantly lower than the rate of the model group (P <0.05),Compared the Shenxuening Jianji group with the Diovan (valsartan) group, there is no statistically significant (P> 0.05).
5、Pathology:
⑴HE staining results: The model group big mouse glomerular is obviously hypertrophy, glomerular mesangial cells hyperplasia with Mesangial matrix increase, Part of glomerular Segmental sclerosis, ball wall adhesion, Renal tubular epithelial cells degeneration, hypertrophy, hyperplasia, Some tubular atrophy, Renal interstitial have varying degrees of mononuclear inflammatory cell infiltration and fibrosis, the Shenxuening Jianji group、the Diovan (valsartan) group compared to the model group is reduced significantly, and the Shenxuening Jianji group than the Diovan (valsartan) group level light.
⑵Immunofluorescence Results: The model group, Shenxuening Jianji group, the Diovan (Valsartan) group big mouse glomerular basement membrane and mesangial area have bright green positive staining deposition, Shenxuening Jianji group, the Diovan (Valsartan) group bright green positive staining deposition less than the model group, and Shenxuening Jianji group bright green positive staining deposition less than the Diovan (Valsartan) group.
⑶Immunohistochemical staining results: In the blank control group kidney organization ,typeⅣCollagen(Col一Ⅳ)has the Mild expression in the glomerular basement membrane and mesangial area, the basement membrane proximal tubular epithelial cells, positive staining for the brown granules ,and in the model group, glomerular basement membrane and mesangial area,renal tubular epithelial cells and the basement membrane mesenchymal show a large number of brown particle deposition. Shenxuening Jianji group, the Diovan (Valsartan) group brown granules deposition is significantly reduced compared to the model group,and Shenxuening Jianji group than the Diovan (Valsartan) group level light.
Conclusion:
1、The Shenxuening Jianji has the function of reducing the IgA nephrosis big mouse 24-hour urine protein and red blood cells, serum creatinine, blood urea nitrogen.
2、The Shenxuening Jianji has the function of reducing the primary IgA nephrosis big mouse expression of typeⅣcollagen.
3、The Shenxuening Jianji has the function of delaying the IgA nephrosis course development. Its mechanism may be by reducing expression of typeⅣcollagen,to reduce the excessive accumulation of ECM, reduce glomerulosclerosis and tubular - interstitial fibrosis, thereby reduce urine protein、hematuria, and Protect renal function.
引文
[1]王海燕.肾脏病学[M].第2版.北京,人民卫生出版社, 1996.708-719.
[2]苗明三.实验动物和动物实验技术[M].北京:中国中医药出版社,2003:142-145.
[3]刘宏伟,等.滋肾止血片对实验性IgA肾病小鼠肾组织氧自由基的影响[J].中国中医基础医学杂志,1996,(6):24-26
[4]Emancipator SN,Gallo GR.Experimen tal IgA nephropathy induced by oral immunization[J].Jexp Med,1983,157:572
[5]刘志红,等.葡萄球菌肠毒素诱发的IgA肾病模型[J].中华肾脏病杂志,1989,5(1):6
[6]Rifai A,et a1.Experimental IgA nephropathy[J].J Exp Med,1979,150(5):1161—1173.
[7]Leung JC,Chan LY,Tsang AW,et a1.Anti-macrophage migration inhibitory factor reduces transforming growth factor-betal expression in experimental IgA nephmpathy [J].Nephrol Dial Transplant,2004,19(8):1976—1985.
[8] Bagheri N,et a1.Development of immunecomplex glomerulone- phritis in athymic mice:T cells are not required for the genesis of glomerular injury[J].Lab Invest,2005,85,(3):354-363.
[9]刘志红.葡萄球菌肠毒素诱发的IgA肾病模型[J].中华肾脏病杂志,1989,5(1):6-10
[10]Gaorge W P. Possible endotoxemia in ribbits after introvecous injection of staphylococcal aureus enterotoxin B [J]. J Infect Dis,1977,135:646
[11]Katre L. Alocholic hepatic disease: Specificity of IgA deposit in liver[J]. Am J Clin Pathol,1977,71:51
[12]Swerdlow MA. Pattern of IgA deposition in liver tissue in alcoholic liver disease[J]. Am J Clin Pathol,1982,77:259
[13]Kutteh W H. Properties of immunoglobulin A in serum of individual with liver disease and in hepatic bile [J]. Gastroenterology,1976,71:985
[14]Suzuki S,et a1.Role of IgA,IgG,and IgM antibodies against Haemophilus parainfluenzae antigens in IgA nephmpathy[J].Clin Nephrol,1996,46(5):287—295.
[15]Yamamoto C , et a1. Experimental nephmpathy induced by Haemophilus parainfluenzae antigens[J].Nephron,2002,90(3):320—327.
[16]Berger J, Hinglais N. Les dép?ts intercapilaires d 'IgA-IgG.J Urol Néphrol,1968, 74(9):694～695.
[17]Donadio JV,Grande JP. IgA nephropathy. N Engl J Med,2002,347(10):738～748.
[18]Rai A,Nast C,Adler S. Henoch-Schonlein purpura nephritis. J Am Soc Nephrol,1999,10(12):2637～2644.
[19]Simon P,et al. Epidemiology of primary glomerular diseases in a French region: variations according to period and age. Kidney Int,1994,46(4): 1192～1198
[20]Wyat RJ,et al. Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994. Central Kentucky Region of the Southeastern United States IgA Nephropathy DATABANK Project. J Am Soc Nephrol,1998,9(5):853～858.
[21]Levy M,Berger J. Worldwide perspective of IgA nephropathy. Am J Kidney Dis,1988,12(5):340～347.
[22]Li LS,Liu ZH. Epidemiologic data of renal diseases from a single unit in China: analysis based on 13,519 renal biopsies. Kidney Int,2004,66(3):920～923.
[23]Cherpillod A,et al. IgA nephropathy:what you have need to know in 2005.Rev Med Suisse,2005,1(8):551～554,556.
[24]解放军肾脏病研究所学术委员会. IgA肾病诊断及治疗规范.肾脏病与透析肾移植杂志,2004,13(3):253～255.
[25]D'Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis,2000,36(2):227～237.
[26]Syrj?nen J,Mustonen J,Pasternack A. Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy.Nephrol Dial Transplant,2000,15(1):34～42.
[27]Couchman JR et al.Glomerular matrix synthesis, tumover and role in mesangial expansion.Kidney Int.1994;45:328
[28]RazzaqueMS, et al. In situ localization of typeⅢand IV collagen expressing cells in human iabetic nephropathy.JPathol,1994;174:131-134
[29]DavidWR, et al. Diabetic glomerulosclerosis immuneog old ultrastructural studies on the glomerular distribution of type IV collagen and Heparan Sulphate Proteoglycan.JPathol,1992;167:49-53
[30]贾明,邹红云,贾保林. 136例Ⅳ型胶原检测结果分析[J] .中国现代医学杂志,2003,13(21):107-108.
[31]陈香美,等。血管紧张素转换酶抑制剂减轻肾小球硬化机制的探讨[J]。中华肾脏病杂志,1998,14:319-142.
[32]Aumailley M. Structure and supramolecular organization of basement memberanes .Kidney Int,1995;47(suppl 49):S4-S7.
[33]鲁盈,等。黄芪当归合剂对肾病综合症血清脂谱和肾小球硬化的影响[J]。中国中西医结合杂志,1997,17(7):478-482.
[34]史跃先,等.解放军医学杂志.1993;18(2):114-117
[35]Wagner C,et al. Interaction of transforming growth factor beta 1 with human glomerular epithelial cells in culture:opposite effects on synthesis of matrix proteins and on urokinase plasminogen activator[J] . J Mol Med,1996,74(3):149-154.
[36]Ten Dijke P,et al. Regulation of cell proliferation by Smad proteins[J] . J Cell physiol,2002,191(1):1-16.
[37]Coimbra T,et al. Transforming growth factorβproduction in anti- glomerular basement membrane disease in the rabbit[J].Am J Pathol,1991(138):223-225.
[38]龚莉,等.肾炎病人血、尿TGF-β1与肾脏纤维化关系的初步研究[J] .内蒙古医学院学报,2005,27(2):77-79.
[39]D'Agati V D,et al. Pathologic classification of focal Segmental glomerulosclerosis,a working proposal[J] . AmJ Kidney Dis,2004,43(2):368-382.
[40]席春生,等.血IVC在肾小球疾病中的变化及临床意义[J] .中国现代医学杂志, 2000, 10(4):66.
[41]李新月,孙燕.肝纤维化患者血清Ⅲ型前胶原、Ⅳ型胶原、透明质酸及层粘蛋白检测[J] .郑州大学学报,2002,27(5):666-667.
[42]史跃先,等. 107例IgA肾病患者肾组织胶原蛋白Ⅳ与肾脏病理关系[J] .解放军医学杂志,1993,18(2):114-117.
[43]刘为民,刘绍能,姚乃礼.肝纤维化络病辨治.中医药研究,2002;18(6):2
[44]蒋宁,武维屏.中医络病学说与肺间质纤维化病机关系初探.中国中医基础医学杂志,2003;9(5):22-23
[45]牛建昭,姜术霞.多脏器纤维化的络病机制探讨.北京中医药大学学报,2004;27(6):4-6
[46]王永炎.关于提高脑血管疾病疗效难点的思考[J].中国中西医结合杂志,1997,17(2):195—196.
[47]雷燕,王永炎,黄启福.络病理论探微[J].北京中医药大学学报,1998,21(2):18—23.
[48]李慧,柴可夫,楼基伟.益肾活血方治疗慢性肾衰的实验研究.浙江中医学院学报,2000,24(6):50—51.
[49]卢祖礼.浅析肾纤维化的中医病机.湖北中医杂志,2004,26(11):18.
[50]于俊生编著.毒邪学说与临床.北京:中国中医药出版社,2000,140-146
[51]王永钧,张敏鸥.痰瘀互结与肾内微型癥积[J].中国中西医结合肾病杂志,2003,4(1):123.
[52]张史昭,潘达亮,丁伟等.肾络瘀阻与肾纤维化关系的临床研究.中国中西医结合肾病杂志,2003,4(8):458-459
[53]穆立芹.肾脏疾病的基因治疗[ J] .国外医学·泌尿系统分册, 2005,25(1) : 104- 108.
[54]Jinde K,Nikolic-Paterson DJ,Huang XR,et a1.Tubular phenotypic change in progressive tubulointerstitial fibrosis in human glomerulonephritis.Am J Kidney Dis,2001,38(4):761
[55]罗海清,粱东,刘华锋.肾间质纤维化的形成机制及中药防治作用.中国中西医结合肾病杂志,2004,5(7):432
[56]魏林,王海燕.细胞外基质在人系膜细胞增生性肾小球肾炎中的变化.中华病理杂志,1994,23:7
[57]KlahrS,et al. The effects of dietary protein restriction and blood pressure control on the progression of chronic renal disease.N Engl J Med,1994,330:877-883.
[58]Rauta V,et al.Factors associated with progression of IgA nephropathy are related to renal function—a model for estimating risk of propathy in mild disease.Clin Nephrol,2003,59(6):481-2
[59]Geddes CC,et al.A tricontinental view IgA nephropathy.Nephrol Dial Transplant,2003,18(8):1541-8
[60]D'Amico G,et al.Typical and atypical natural history of IgA nephropathy in adult patients.Contrib Nephrol,1993,104:6-13
[61]夏春英,陈力,孟羽贤.黄芪对慢性肾炎的红细胞免疫功能及IL-6的影响.中国中医药科技,1997,4(5):263.
[62]余凌,等.黄芪当归在肾脏疾病中的应用及其机制研究进展.中国中西医结合杂志,2001;21(5):396-399.
[63]倪兆慧,等.黄芪对人肾小球系膜细胞CD44 RNA表达的影响.中国中西医结合肾病杂志,2001,2(1):13-16.
[64]黄海长,等.结缔组织生长因子诱导成纤维细胞转化为成肌纤维细胞[J].科学通报,2002,47(1):37240.
[65]韦颖,等.三七总甙对肾成纤维细胞的影响.中国中西医结合杂志,2002 ,22 (1) :47.
[66]杜兰屏,等.莪术对肾脏细胞外基质影响的实验研究.上海中医药杂志,2001,35(6):38
[67]张翠,康广盛,刘薇.含大黄、水蛭等中药复方对肾大部切除大鼠肾脏保护作用的研究.中国实验方剂学杂志,2004,10(1):31
[1]王海燕.肾脏病学[M].第2版.北京,人民卫生出版社, 1996.708-719.
[2]Couchman JR et al.Glomerular matrix synthesis, tumover and role in mesangial expansion.Kidney Int.1994;45:328
[3]Hudson J et al. J Biol Chem ,1993;15:26033-26036
[4]刘秉慈,许增禄..细胞外间质.生理科学进展,1996,27(3):221-226
[5]周爱儒,查锡良.生物化学.北京:人民卫生出版社,2002,406-413
[6]Pratt BM, Form D, Madri JA. Endothelial cell-extracellular Matrix intaractions. Ann NYA cad Sci, 1985, 460:274-288.
[7]陈光等.胶原蛋白对毛细血管瘤病理演变的影响。中华小儿外科杂志,1998(6):329-330。
[8]韩承新.血管瘤增生退化机制的研究进展,中华小儿外科, 1995,10(5):309-311。
[9]林晓萍.婴幼儿血管瘤中bFGF与细胞外基质相关关系的研究,中国医科大学学报,28(2):128-131。
[10]Liotta LA, Rao CN, Barsky SH. Tumor invasion and the extracellular matrix. Lab Invest,1983,49:636.
[11]EngE, et al. Does extracellular matrix expansion in golmerular disease require mesangial cell proliferation. KidneyInt,1994,45:S45-47
[12]KimY, et al. Differential expression of basement membrane collagen chains in diabetic nephropathy. Am J Pathol,1991,138:413
[13]Stelfes MW, et al. Cell and matrix components of the glomerular mesangium in type l diabetes. Diabetes,1992,41:679
[14]魏林,王海燕.细胞外基质在人系膜细胞增生性肾小球肾炎中的变化.中华病理杂志,1994,23:7
[15]Aumailley M. Structure and supramolecular organization of basement memberanes. Kidney Int,1995,7(suppl49):S4-S7
[16]FalkRJ, et al.Polyantigenic expansion of basement membrane Constituents in diabetic nephropathy.Diabetes,1983;32:34-38.
[17]YagameM, et al.Differential distribution of type IV collangen chains in patients with diabetic nephropathy in noninsulin-dependent diabetesm mellitus.Nephron,1995;70:42-46
[18]KimY, et al.Differential expression of basement membrane collagen chains in diabetic nephropathy.AmJPathol,1991;138:413-417
[19]ZhuD, et al.Glomerular distribution of extracellular matrix components in insulin dependent diabetes by high resolution quantitative immunochemistry. J Am Soc Nephrol,1992;3:770-782
[20]Wu K, et al. Altered kidney matrix gene expression in early stages of experimental diabetes. Acta Anat Basel,1997,158(3):155-165.
[21]邹燕勤,章永红.IgA肾病的中医治疗.中华肾脏病杂志,1992,8(4):235-236
[22]聂莉芳.IgA肾病血尿的中医药辨治[J].中国中西医结合肾病杂志,2001,2(11):621
[23]杜治宏.杜雨茂教授治疗IgA肾病的经验.现代中医药,2005.(2):1
[24]朱良伟,等.中西医结合治疗IgA肾病23例临床观察[J].浙江中西医结合杂志,1998,8(4):204—205
[25]卢巧珍.陈以平治疗IgA肾病的经验.中医文献杂志,2004.(2):40.
[26]孙伟.IgA肾病中医病理机制的探讨EJ].河北中西医结合杂志,1999,8(4);522.
[27]马红梅,黄文政,胡晓蕙.中药肾炎3号方对小鼠实验性IgA肾病红细胞免疫动态研究.中国实验临床免疫学杂志,1995,7(4):42-44
[28]都占陶.肾炎血尿康治疗IgA肾病的临床及实验研究.中国中医药科技,1994,1(1):19
[29]文蓉珠,关广聚,管益君.冬虫夏草对IgA肾病小鼠腹腔巨噬细胞功能的影响.山东医科大学学报,2000,38(2):221-222
[30]张铎,等.中西医结合治疗IgA肾病临床观察.内蒙古中医药,2000,19(2):18-20
[31]洪江淮,等.小蓟饮子加减治疗标证为湿热型的IgA肾病疗效观察.福建中医药,2000,31(2):11-13
[32]杨志云,马琼英.丹参注射液对肾小球系膜细胞增殖及产生IL-6、Ⅳ型胶原影响的实验研究.中国中西医结合肾病杂志2001;2(7):420
[33]王军,等.复方积雪草对局灶硬化性肾小球肾炎模型小鼠肾组织内细胞因子表达的调控作用[J].中国临床药理学与治疗学,2003,8(6):638-641 [34[阳晓,魏毅.补肾清利活血法对大鼠残肾细胞基质影响的实验研究[J].中国中西医结合杂志,2000,20(10):767-770
[35]张俊峰,等.黄芪当归合剂对肾病综合征鼠肾组织表型变化的影响[J].山西中医,2001,16(2):41-42
[36]鲁盈,等.黄芪当归合剂对肾病综合症血清脂谱和肾小球硬化的影响[J]。中国中西医结合杂志,1997,17(7):478-482.
[37]史跃先,等.解放军医学杂志.1993;18(2):114-117
[2]苗明三.实验动物和动物实验技术[M].北京:中国中医药出版社,2003:142-145.
[3]刘宏伟,等.滋肾止血片对实验性IgA肾病小鼠肾组织氧自由基的影响[J].中国中医基础医学杂志,1996,(6):24-26
[4]Emancipator SN,Gallo GR.Experimen tal IgA nephropathy induced by oral immunization[J].Jexp Med,1983,157:572
[5]刘志红,等.葡萄球菌肠毒素诱发的IgA肾病模型[J].中华肾脏病杂志,1989,5(1):6
[6]Rifai A,et a1.Experimental IgA nephropathy[J].J Exp Med,1979,150(5):1161—1173.
[7]Leung JC,Chan LY,Tsang AW,et a1.Anti-macrophage migration inhibitory factor reduces transforming growth factor-betal expression in experimental IgA nephmpathy [J].Nephrol Dial Transplant,2004,19(8):1976—1985.
[8] Bagheri N,et a1.Development of immunecomplex glomerulone- phritis in athymic mice:T cells are not required for the genesis of glomerular injury[J].Lab Invest,2005,85,(3):354-363.
[9]刘志红.葡萄球菌肠毒素诱发的IgA肾病模型[J].中华肾脏病杂志,1989,5(1):6-10
[10]Gaorge W P. Possible endotoxemia in ribbits after introvecous injection of staphylococcal aureus enterotoxin B [J]. J Infect Dis,1977,135:646
[11]Katre L. Alocholic hepatic disease: Specificity of IgA deposit in liver[J]. Am J Clin Pathol,1977,71:51
[12]Swerdlow MA. Pattern of IgA deposition in liver tissue in alcoholic liver disease[J]. Am J Clin Pathol,1982,77:259
[13]Kutteh W H. Properties of immunoglobulin A in serum of individual with liver disease and in hepatic bile [J]. Gastroenterology,1976,71:985
[14]Suzuki S,et a1.Role of IgA,IgG,and IgM antibodies against Haemophilus parainfluenzae antigens in IgA nephmpathy[J].Clin Nephrol,1996,46(5):287—295.
[15]Yamamoto C , et a1. Experimental nephmpathy induced by Haemophilus parainfluenzae antigens[J].Nephron,2002,90(3):320—327.
[16]Berger J, Hinglais N. Les dép?ts intercapilaires d 'IgA-IgG.J Urol Néphrol,1968, 74(9):694～695.
[17]Donadio JV,Grande JP. IgA nephropathy. N Engl J Med,2002,347(10):738～748.
[18]Rai A,Nast C,Adler S. Henoch-Schonlein purpura nephritis. J Am Soc Nephrol,1999,10(12):2637～2644.
[19]Simon P,et al. Epidemiology of primary glomerular diseases in a French region: variations according to period and age. Kidney Int,1994,46(4): 1192～1198
[20]Wyat RJ,et al. Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994. Central Kentucky Region of the Southeastern United States IgA Nephropathy DATABANK Project. J Am Soc Nephrol,1998,9(5):853～858.
[21]Levy M,Berger J. Worldwide perspective of IgA nephropathy. Am J Kidney Dis,1988,12(5):340～347.
[22]Li LS,Liu ZH. Epidemiologic data of renal diseases from a single unit in China: analysis based on 13,519 renal biopsies. Kidney Int,2004,66(3):920～923.
[23]Cherpillod A,et al. IgA nephropathy:what you have need to know in 2005.Rev Med Suisse,2005,1(8):551～554,556.
[24]解放军肾脏病研究所学术委员会. IgA肾病诊断及治疗规范.肾脏病与透析肾移植杂志,2004,13(3):253～255.
[25]D'Amico G. Natural history of idiopathic IgA nephropathy: role of clinical and histological prognostic factors. Am J Kidney Dis,2000,36(2):227～237.
[26]Syrj?nen J,Mustonen J,Pasternack A. Hypertriglyceridaemia and hyperuricaemia are risk factors for progression of IgA nephropathy.Nephrol Dial Transplant,2000,15(1):34～42.
[27]Couchman JR et al.Glomerular matrix synthesis, tumover and role in mesangial expansion.Kidney Int.1994;45:328
[28]RazzaqueMS, et al. In situ localization of typeⅢand IV collagen expressing cells in human iabetic nephropathy.JPathol,1994;174:131-134
[29]DavidWR, et al. Diabetic glomerulosclerosis immuneog old ultrastructural studies on the glomerular distribution of type IV collagen and Heparan Sulphate Proteoglycan.JPathol,1992;167:49-53
[30]贾明,邹红云,贾保林. 136例Ⅳ型胶原检测结果分析[J] .中国现代医学杂志,2003,13(21):107-108.
[31]陈香美,等。血管紧张素转换酶抑制剂减轻肾小球硬化机制的探讨[J]。中华肾脏病杂志,1998,14:319-142.
[32]Aumailley M. Structure and supramolecular organization of basement memberanes .Kidney Int,1995;47(suppl 49):S4-S7.
[33]鲁盈,等。黄芪当归合剂对肾病综合症血清脂谱和肾小球硬化的影响[J]。中国中西医结合杂志,1997,17(7):478-482.
[34]史跃先,等.解放军医学杂志.1993;18(2):114-117
[35]Wagner C,et al. Interaction of transforming growth factor beta 1 with human glomerular epithelial cells in culture:opposite effects on synthesis of matrix proteins and on urokinase plasminogen activator[J] . J Mol Med,1996,74(3):149-154.
[36]Ten Dijke P,et al. Regulation of cell proliferation by Smad proteins[J] . J Cell physiol,2002,191(1):1-16.
[37]Coimbra T,et al. Transforming growth factorβproduction in anti- glomerular basement membrane disease in the rabbit[J].Am J Pathol,1991(138):223-225.
[38]龚莉,等.肾炎病人血、尿TGF-β1与肾脏纤维化关系的初步研究[J] .内蒙古医学院学报,2005,27(2):77-79.
[39]D'Agati V D,et al. Pathologic classification of focal Segmental glomerulosclerosis,a working proposal[J] . AmJ Kidney Dis,2004,43(2):368-382.
[40]席春生,等.血IVC在肾小球疾病中的变化及临床意义[J] .中国现代医学杂志, 2000, 10(4):66.
[41]李新月,孙燕.肝纤维化患者血清Ⅲ型前胶原、Ⅳ型胶原、透明质酸及层粘蛋白检测[J] .郑州大学学报,2002,27(5):666-667.
[42]史跃先,等. 107例IgA肾病患者肾组织胶原蛋白Ⅳ与肾脏病理关系[J] .解放军医学杂志,1993,18(2):114-117.
[43]刘为民,刘绍能,姚乃礼.肝纤维化络病辨治.中医药研究,2002;18(6):2
[44]蒋宁,武维屏.中医络病学说与肺间质纤维化病机关系初探.中国中医基础医学杂志,2003;9(5):22-23
[45]牛建昭,姜术霞.多脏器纤维化的络病机制探讨.北京中医药大学学报,2004;27(6):4-6
[46]王永炎.关于提高脑血管疾病疗效难点的思考[J].中国中西医结合杂志,1997,17(2):195—196.
[47]雷燕,王永炎,黄启福.络病理论探微[J].北京中医药大学学报,1998,21(2):18—23.
[48]李慧,柴可夫,楼基伟.益肾活血方治疗慢性肾衰的实验研究.浙江中医学院学报,2000,24(6):50—51.
[49]卢祖礼.浅析肾纤维化的中医病机.湖北中医杂志,2004,26(11):18.
[50]于俊生编著.毒邪学说与临床.北京:中国中医药出版社,2000,140-146
[51]王永钧,张敏鸥.痰瘀互结与肾内微型癥积[J].中国中西医结合肾病杂志,2003,4(1):123.
[52]张史昭,潘达亮,丁伟等.肾络瘀阻与肾纤维化关系的临床研究.中国中西医结合肾病杂志,2003,4(8):458-459
[53]穆立芹.肾脏疾病的基因治疗[ J] .国外医学·泌尿系统分册, 2005,25(1) : 104- 108.
[54]Jinde K,Nikolic-Paterson DJ,Huang XR,et a1.Tubular phenotypic change in progressive tubulointerstitial fibrosis in human glomerulonephritis.Am J Kidney Dis,2001,38(4):761
[55]罗海清,粱东,刘华锋.肾间质纤维化的形成机制及中药防治作用.中国中西医结合肾病杂志,2004,5(7):432
[56]魏林,王海燕.细胞外基质在人系膜细胞增生性肾小球肾炎中的变化.中华病理杂志,1994,23:7
[57]KlahrS,et al. The effects of dietary protein restriction and blood pressure control on the progression of chronic renal disease.N Engl J Med,1994,330:877-883.
[58]Rauta V,et al.Factors associated with progression of IgA nephropathy are related to renal function—a model for estimating risk of propathy in mild disease.Clin Nephrol,2003,59(6):481-2
[59]Geddes CC,et al.A tricontinental view IgA nephropathy.Nephrol Dial Transplant,2003,18(8):1541-8
[60]D'Amico G,et al.Typical and atypical natural history of IgA nephropathy in adult patients.Contrib Nephrol,1993,104:6-13
[61]夏春英,陈力,孟羽贤.黄芪对慢性肾炎的红细胞免疫功能及IL-6的影响.中国中医药科技,1997,4(5):263.
[62]余凌,等.黄芪当归在肾脏疾病中的应用及其机制研究进展.中国中西医结合杂志,2001;21(5):396-399.
[63]倪兆慧,等.黄芪对人肾小球系膜细胞CD44 RNA表达的影响.中国中西医结合肾病杂志,2001,2(1):13-16.
[64]黄海长,等.结缔组织生长因子诱导成纤维细胞转化为成肌纤维细胞[J].科学通报,2002,47(1):37240.
[65]韦颖,等.三七总甙对肾成纤维细胞的影响.中国中西医结合杂志,2002 ,22 (1) :47.
[66]杜兰屏,等.莪术对肾脏细胞外基质影响的实验研究.上海中医药杂志,2001,35(6):38
[67]张翠,康广盛,刘薇.含大黄、水蛭等中药复方对肾大部切除大鼠肾脏保护作用的研究.中国实验方剂学杂志,2004,10(1):31
[1]王海燕.肾脏病学[M].第2版.北京,人民卫生出版社, 1996.708-719.
[2]Couchman JR et al.Glomerular matrix synthesis, tumover and role in mesangial expansion.Kidney Int.1994;45:328
[3]Hudson J et al. J Biol Chem ,1993;15:26033-26036
[4]刘秉慈,许增禄..细胞外间质.生理科学进展,1996,27(3):221-226
[5]周爱儒,查锡良.生物化学.北京:人民卫生出版社,2002,406-413
[6]Pratt BM, Form D, Madri JA. Endothelial cell-extracellular Matrix intaractions. Ann NYA cad Sci, 1985, 460:274-288.
[7]陈光等.胶原蛋白对毛细血管瘤病理演变的影响。中华小儿外科杂志,1998(6):329-330。
[8]韩承新.血管瘤增生退化机制的研究进展,中华小儿外科, 1995,10(5):309-311。
[9]林晓萍.婴幼儿血管瘤中bFGF与细胞外基质相关关系的研究,中国医科大学学报,28(2):128-131。
[10]Liotta LA, Rao CN, Barsky SH. Tumor invasion and the extracellular matrix. Lab Invest,1983,49:636.
[11]EngE, et al. Does extracellular matrix expansion in golmerular disease require mesangial cell proliferation. KidneyInt,1994,45:S45-47
[12]KimY, et al. Differential expression of basement membrane collagen chains in diabetic nephropathy. Am J Pathol,1991,138:413
[13]Stelfes MW, et al. Cell and matrix components of the glomerular mesangium in type l diabetes. Diabetes,1992,41:679
[14]魏林,王海燕.细胞外基质在人系膜细胞增生性肾小球肾炎中的变化.中华病理杂志,1994,23:7
[15]Aumailley M. Structure and supramolecular organization of basement memberanes. Kidney Int,1995,7(suppl49):S4-S7
[16]FalkRJ, et al.Polyantigenic expansion of basement membrane Constituents in diabetic nephropathy.Diabetes,1983;32:34-38.
[17]YagameM, et al.Differential distribution of type IV collangen chains in patients with diabetic nephropathy in noninsulin-dependent diabetesm mellitus.Nephron,1995;70:42-46
[18]KimY, et al.Differential expression of basement membrane collagen chains in diabetic nephropathy.AmJPathol,1991;138:413-417
[19]ZhuD, et al.Glomerular distribution of extracellular matrix components in insulin dependent diabetes by high resolution quantitative immunochemistry. J Am Soc Nephrol,1992;3:770-782
[20]Wu K, et al. Altered kidney matrix gene expression in early stages of experimental diabetes. Acta Anat Basel,1997,158(3):155-165.
[21]邹燕勤,章永红.IgA肾病的中医治疗.中华肾脏病杂志,1992,8(4):235-236
[22]聂莉芳.IgA肾病血尿的中医药辨治[J].中国中西医结合肾病杂志,2001,2(11):621
[23]杜治宏.杜雨茂教授治疗IgA肾病的经验.现代中医药,2005.(2):1
[24]朱良伟,等.中西医结合治疗IgA肾病23例临床观察[J].浙江中西医结合杂志,1998,8(4):204—205
[25]卢巧珍.陈以平治疗IgA肾病的经验.中医文献杂志,2004.(2):40.
[26]孙伟.IgA肾病中医病理机制的探讨EJ].河北中西医结合杂志,1999,8(4);522.
[27]马红梅,黄文政,胡晓蕙.中药肾炎3号方对小鼠实验性IgA肾病红细胞免疫动态研究.中国实验临床免疫学杂志,1995,7(4):42-44
[28]都占陶.肾炎血尿康治疗IgA肾病的临床及实验研究.中国中医药科技,1994,1(1):19
[29]文蓉珠,关广聚,管益君.冬虫夏草对IgA肾病小鼠腹腔巨噬细胞功能的影响.山东医科大学学报,2000,38(2):221-222
[30]张铎,等.中西医结合治疗IgA肾病临床观察.内蒙古中医药,2000,19(2):18-20
[31]洪江淮,等.小蓟饮子加减治疗标证为湿热型的IgA肾病疗效观察.福建中医药,2000,31(2):11-13
[32]杨志云,马琼英.丹参注射液对肾小球系膜细胞增殖及产生IL-6、Ⅳ型胶原影响的实验研究.中国中西医结合肾病杂志2001;2(7):420
[33]王军,等.复方积雪草对局灶硬化性肾小球肾炎模型小鼠肾组织内细胞因子表达的调控作用[J].中国临床药理学与治疗学,2003,8(6):638-641 [34[阳晓,魏毅.补肾清利活血法对大鼠残肾细胞基质影响的实验研究[J].中国中西医结合杂志,2000,20(10):767-770
[35]张俊峰,等.黄芪当归合剂对肾病综合征鼠肾组织表型变化的影响[J].山西中医,2001,16(2):41-42
[36]鲁盈,等.黄芪当归合剂对肾病综合症血清脂谱和肾小球硬化的影响[J]。中国中西医结合杂志,1997,17(7):478-482.
[37]史跃先,等.解放军医学杂志.1993;18(2):114-117