基于玄府理论的固本通络方对IgA肾病大鼠Nephrin和CD_2AP表达的影响
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摘要
目的:观察固本通络方对IgA肾病大鼠肾小球足细胞Nephrin和CD_2AP表达的影响。方法:采用牛血清白蛋白(BSA)+四氯化碳(CCl4)+蓖麻油(CO)+脂多糖(LPS)的方法建立IgAN大鼠模型,分为正常组、模型组、中药组和氯沙坦钾组,治疗4周后,检测各组大鼠24 h尿蛋白量,观察肾小球形态学变化,并采用免疫组化和实时定量PCR法检测肾小球足细胞Nephrin和CD_2AP的蛋白及mRNA表达。结果:与正常组比较,模型组大鼠24 h尿蛋白量显著升高(P<0.01),肾小球系膜增生,足突融合明显,足细胞Nephrin和CD_2AP的蛋白及mRNA表达均明显下调(P<0.01);经固本通络方治疗后上述指标均明显改善,与模型组比较差异有统计学意义(P<0.01)。结论:固本通络方能减轻IgAN大鼠蛋白尿及肾小球病变并具有一定的时效关系,其作用可能与调节肾小球足细胞Nephrin、CD_2AP的表达有关。
Objective: To observe the effects of"Guben Tongluo Formula"on expression of Nephrin and CD_2AP in glomerular podocytes in IgA nephropathy rats. Methods: The SPF male SD rats were randomly divided into four groups: normal group,model group,herb group and Losartan potassium group. With the method of Bovine serum albumin( BSA) + carbon tetrachloride( CCl4)+ lipopolysaccharide( LPS) establishing rat model of IgAN. All groups were treated accordingly. At the end of 4 th week,the levels of 24-hour urinary protein( Upr) were measured; the pathological changes of glomeruliwere observed,and the immunohistochemistry and real-time quantitative PCR were used respectively to examine the protein and mRNA expression of Nephrin and CD_2AP in glomerul. Results: Compared with the normal group,Upr,mesangial cells and mesangial matrix were increased significantly in model group( P < 0. 01); foot processes fusion was observed,and the protein and mRNA expression of Nephrin and CD_2AP in glomerular podocytes were reduced significantly( P < 0. 01). Compared with the model group,all the indicators above improved remarkably in herb group( P < 0. 01). Conclusion: "Guben Tongluo Formula"can relieve the proteinuria and glomerulopathy in rats of IgA nephropathy by elevating the expression of Nephrin and CD_2AP in podocyte.
Objective: To observe the effects of"Guben Tongluo Formula"on expression of Nephrin and CD_2AP in glomerular podocytes in IgA nephropathy rats. Methods: The SPF male SD rats were randomly divided into four groups: normal group,model group,herb group and Losartan potassium group. With the method of Bovine serum albumin( BSA) + carbon tetrachloride( CCl4)+ lipopolysaccharide( LPS) establishing rat model of IgAN. All groups were treated accordingly. At the end of 4 th week,the levels of 24-hour urinary protein( Upr) were measured; the pathological changes of glomeruliwere observed,and the immunohistochemistry and real-time quantitative PCR were used respectively to examine the protein and mRNA expression of Nephrin and CD_2AP in glomerul. Results: Compared with the normal group,Upr,mesangial cells and mesangial matrix were increased significantly in model group( P < 0. 01); foot processes fusion was observed,and the protein and mRNA expression of Nephrin and CD_2AP in glomerular podocytes were reduced significantly( P < 0. 01). Compared with the model group,all the indicators above improved remarkably in herb group( P < 0. 01). Conclusion: "Guben Tongluo Formula"can relieve the proteinuria and glomerulopathy in rats of IgA nephropathy by elevating the expression of Nephrin and CD_2AP in podocyte.
引文
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3 .汤颖,娄探奇,成彩联,等.实验性Ig A肾病模型的改进.中山大学学报,2006,27(2):184-187.
4 .刘玉园,刘虹,柴华旗.Ig A肾病肾损伤机制研究进展.中国中西医结合肾病杂志,2016,17(1):79-81.
5 .Goto M,Wakai K,Kawamura T,et al.A scoring system to predict renal outcome in Ig A nephropathy:a nationwide 10-year prospective cohortstudy.Nephrol Dial Transplant,2009,24(10):3068-3074.
6 .Berthoux F,Mohey H,Laurent B,et al.Predicting the Risk for Dialysis or Death in Ig A Nephropathy.J Am Soc Nephrol,2011,22(4):752-761.
7 .Durvasula RV,Shankland SJ.Podocyte injury and targeting therapy:an update.Curr Opin Nephrol Hypertens,2006,15(1):1-7.
8 .Kalluri R.Proteinuria with and without renal glomerular podocyte effacement.J am Soc Nephrol,2006,17(9):2383-2389.
9 .Zhang A,Huang S.Progress in pathogenesis of proteinuria.International journal of nephrology,2012.
10 .罗再琼,黄文强,杨九一.“玄府”:藏象理论的微观结构.中医杂志,2011,52(16):1354-1356.
11 .Aaltonen P,Luimula P,Astr m E,et al.Changes in the expression of nephrin gene and protein in experimental diabetic nephropathy.Lab Invest,2001,81(9):1185-1190.
12 .唐英,蒋宇锋,邹赟,等.Ig A肾病足细胞损伤机制及中医药治疗的研究进展,中国中西医结合肾病杂志,2016,17(8):744-746.
13 .郑平东,周家俊,高建东,等.固本通络冲剂治疗Ig A肾病的临床疗效观察,中国中西医结合肾病杂志,2003,4(3):150-152.
14 .周家俊,高建东,何立群,等.固本通络冲剂治疗Ig A肾病的实验研究.中国中西医结合肾病杂志,2003,4(8):442-444.
2 .Barratt J,Feehally J.Ig A nephropathy.J Am Soc Nephrol,2005,16(7):2088-2097.
3 .汤颖,娄探奇,成彩联,等.实验性Ig A肾病模型的改进.中山大学学报,2006,27(2):184-187.
4 .刘玉园,刘虹,柴华旗.Ig A肾病肾损伤机制研究进展.中国中西医结合肾病杂志,2016,17(1):79-81.
5 .Goto M,Wakai K,Kawamura T,et al.A scoring system to predict renal outcome in Ig A nephropathy:a nationwide 10-year prospective cohortstudy.Nephrol Dial Transplant,2009,24(10):3068-3074.
6 .Berthoux F,Mohey H,Laurent B,et al.Predicting the Risk for Dialysis or Death in Ig A Nephropathy.J Am Soc Nephrol,2011,22(4):752-761.
7 .Durvasula RV,Shankland SJ.Podocyte injury and targeting therapy:an update.Curr Opin Nephrol Hypertens,2006,15(1):1-7.
8 .Kalluri R.Proteinuria with and without renal glomerular podocyte effacement.J am Soc Nephrol,2006,17(9):2383-2389.
9 .Zhang A,Huang S.Progress in pathogenesis of proteinuria.International journal of nephrology,2012.
10 .罗再琼,黄文强,杨九一.“玄府”:藏象理论的微观结构.中医杂志,2011,52(16):1354-1356.
11 .Aaltonen P,Luimula P,Astr m E,et al.Changes in the expression of nephrin gene and protein in experimental diabetic nephropathy.Lab Invest,2001,81(9):1185-1190.
12 .唐英,蒋宇锋,邹赟,等.Ig A肾病足细胞损伤机制及中医药治疗的研究进展,中国中西医结合肾病杂志,2016,17(8):744-746.
13 .郑平东,周家俊,高建东,等.固本通络冲剂治疗Ig A肾病的临床疗效观察,中国中西医结合肾病杂志,2003,4(3):150-152.
14 .周家俊,高建东,何立群,等.固本通络冲剂治疗Ig A肾病的实验研究.中国中西医结合肾病杂志,2003,4(8):442-444.