肾复康Ⅵ号治疗肾病综合征大鼠模型疗效及分子通道选择性效应
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摘要
目的:研究肾复康Ⅵ号对阿霉素大鼠模型的肾小球滤过膜中构成裂孔隔膜骨架的其中两种蛋白nephrin、podocin的变化,探讨肾复康Ⅵ号、激素泼尼松及其二者联合使用对阿霉素大鼠模型的疗效及影响。方法:大鼠60只分为5组:正常组、模型组、中药组、西药组和中西医结合组,每组各12只。除正常组,各组大鼠尾静脉一次性注射阿霉素,正常组大鼠尾静脉一次性注射等剂量生理盐水,在造模成功后给予中药组肾复康Ⅵ号、西药组泼尼松、中西医结合组泼尼松和肾复康Ⅵ号灌胃干预4周,各组大鼠每周检测24 h尿蛋白定量。于给药4周结束后检测大鼠血生化指标,采集肾脏标本,采取免疫组织化学检测大鼠肾小球中nephrin、podocin的变化和分布改变,对大鼠肾脏标本于光镜下观察病理改变。结果:与正常组比较,其它各组尿蛋白升高明显(P<0.05),血白蛋白含量降低明显(P<0.05);与模型组比较,各治疗组尿蛋白下降明显(P<0.05);血白蛋白含量部分用药组升高(P<0.05);光镜下观察各组肾小球结构无明显差异。免疫组化结果:与正常组相比其他各组nephrin、podocin表达数量有所减少(P<0.05),与模型组相比,各治疗组中nephrin表达除中药组外其它两组高于模型组(P<0.05),各治疗组中podocin表达西药组高于模型组(P<0.05),其他两组与模型组相比无统计学意义(P>0.05);与正常组比较,nephrin、podocin沿肾小球毛细血管袢呈线性分布,其他各组中nephrin、podocin呈片状、不连续性颗粒样分布;与模型组比较,各治疗组nephrin、podocin蛋白分布情况无明显差别。结论:肾复康Ⅵ方能够减少阿霉素大鼠24 h尿蛋白定量;肾复康Ⅵ号使阿霉素大鼠减少的nephrin蛋白表达得以部分恢复,减少的podocin蛋白表达得以部分升高,其在肾小球滤过膜中的分布异常改善不明显。
Objective:To study the effect of Shenfukang Ⅵ on nephrin and podocin in glomerular filtration membrane of adriamycin rat model,and to investigate the effect of Shenfukang Ⅵ,prednisone and their combination on adriamycin rat model. Methods:60 rats were divided into 5 groups:normal group,model group,traditional Chinese medicine group,Western medicine group and integrated Chinese and Western medicine group. There were 12 rats in each group. In addition to the normal group,the rats in each group were injected with adriamycin in the tail vein at one time,and the rats in the normal group were injected with the same dose of physiological saline in the tail vein at one time. The rats in the Chinese medicine group and the Western medicine group were given Shenfukang Ⅵ in the second week of the experiment. Prednisone and Shenfukang Ⅵ were given orally for 4 weeks in the group of integrated traditional Chinese and Western medicine. 24 h urine protein was measured every week. Detection of blood biochemical indexes in rats after 4 weeks of administration,the blood biochemical indexes of rats were detected,and the renal samples were collected. The changes and distribution of nephrininpodocin in rat glomeruli were detected by immunohistochemistry,and the pathological changes were observed under light microscope.Results:The results showed that the urinary protein in the kidney of rats was significantly higher than that in the normal group(P<0.05),and the content of serum albumin decreased(P<0.05). Compared with model group,the urinary protein of each treatment group decreased significantly(P<0.05). The content of serum albumin increased(P<0.05). Compared with the model group,the expression of nephrin in each treatment group was higher than that in the model group(P<0.05). The expression of podocin in each treatment group was higher than that in the model group(P<0.05). Compared with the normal group,nephrin,podocin showed a linear distribution along the glomerular capillary loop,and nephrin,podocin in other groups was in the form of sheet-like,discontinuous particle sample. Compared with model group,there was no significant difference in nephrin,podocin protein distribution in each treatment group. Conclusion:Shenfukang Ⅵ can reduce the amount of urinary protein 24 hours in adriamycin-induced rats. The expression of nephrin protein decreased partially,and the expression of podocin protein was partially increased,and its distribution in glomerular filtration membrane was not significantly improved. Conclusion:Shenfukang Ⅵ prescription can reduce the 24 h urinary protein quantity of adriamycin rats,Shenfukang Ⅵ can partially restore the reduced nephrin protein expression and increase the reduced podocin protein expression in rats. The abnormal distribution in glomerular filtration membrane was not significantly improved.
Objective:To study the effect of Shenfukang Ⅵ on nephrin and podocin in glomerular filtration membrane of adriamycin rat model,and to investigate the effect of Shenfukang Ⅵ,prednisone and their combination on adriamycin rat model. Methods:60 rats were divided into 5 groups:normal group,model group,traditional Chinese medicine group,Western medicine group and integrated Chinese and Western medicine group. There were 12 rats in each group. In addition to the normal group,the rats in each group were injected with adriamycin in the tail vein at one time,and the rats in the normal group were injected with the same dose of physiological saline in the tail vein at one time. The rats in the Chinese medicine group and the Western medicine group were given Shenfukang Ⅵ in the second week of the experiment. Prednisone and Shenfukang Ⅵ were given orally for 4 weeks in the group of integrated traditional Chinese and Western medicine. 24 h urine protein was measured every week. Detection of blood biochemical indexes in rats after 4 weeks of administration,the blood biochemical indexes of rats were detected,and the renal samples were collected. The changes and distribution of nephrininpodocin in rat glomeruli were detected by immunohistochemistry,and the pathological changes were observed under light microscope.Results:The results showed that the urinary protein in the kidney of rats was significantly higher than that in the normal group(P<0.05),and the content of serum albumin decreased(P<0.05). Compared with model group,the urinary protein of each treatment group decreased significantly(P<0.05). The content of serum albumin increased(P<0.05). Compared with the model group,the expression of nephrin in each treatment group was higher than that in the model group(P<0.05). The expression of podocin in each treatment group was higher than that in the model group(P<0.05). Compared with the normal group,nephrin,podocin showed a linear distribution along the glomerular capillary loop,and nephrin,podocin in other groups was in the form of sheet-like,discontinuous particle sample. Compared with model group,there was no significant difference in nephrin,podocin protein distribution in each treatment group. Conclusion:Shenfukang Ⅵ can reduce the amount of urinary protein 24 hours in adriamycin-induced rats. The expression of nephrin protein decreased partially,and the expression of podocin protein was partially increased,and its distribution in glomerular filtration membrane was not significantly improved. Conclusion:Shenfukang Ⅵ prescription can reduce the 24 h urinary protein quantity of adriamycin rats,Shenfukang Ⅵ can partially restore the reduced nephrin protein expression and increase the reduced podocin protein expression in rats. The abnormal distribution in glomerular filtration membrane was not significantly improved.
引文
[1]彭亚琴,莫樱,蒋小云,等.阿霉素肾病大鼠肾组织中nephrin和CD2AP的表达及意义[J].中山大学学报:医学科学版,2009,30(1):15-20.
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[3]Danziger J.Importance of low-grade albuminuria[J].Mayo Clin Proc,2008,83(7):806-812.
[4]林跃辉,嵇美霞,胡岗,等.加味参芪地黄汤辅助治疗糖尿病肾病临床观察[J].浙江中西医结合杂志,2010,20(11):679-680.
[5]白晓红,赵历军.中药肾复康对肾病患儿血清皮质醇的影响[J].辽宁中医药大学学报,2013(2):18-19.
[6]余凌,李惊子,王海燕.黄芪、当归在肾脏疾病中的应用及其机制研究进展[J].中国中西医结合杂志,2001,21(5):396-399.
[7]余凌,张峻峰,李惊子,等.黄芪当归合剂防治肾病综合征鼠进行性肾小管间质损伤[J].中华肾脏病杂志,2000,16(5):282-286.
[8]陆海英,张悦,刘煜敏,等.丹参酚酸B对肾纤维化大鼠肾组织MMP-2表达的影响[J].上海中医药大学学报,2009,23(2):55-58.
[9]王军建,胡锐.丹参酮ⅡA对阿霉素肾病大鼠肾小球nephrin和TGF-β1的表达影响[J].中国实验方剂学杂志,2011,17(19):245-251.
[10]Kim SK.Protective effect of Tanshinone IIA on the early stage of experimental diabetic nephropathy[J].Pharmaceutical Bulletin,2009,32(2):220-224.
[11]Zeisberg M,Bonner G,Maeshima Y,et al.Renal fibrosis:collagen composition and assembly regulates epithelialmesenchymal transdifferentiation[J].The American journal of pathology,2001,159(4):1313-1321.
[12]Kim uraM,AsanoM,AbeK,et al.Role of atrophic changes in proximal tubular cells in the per itubular deposition of typel collagen in a ratrenal ablation model[J].Nephrol Dial Transplant,2005,20(8):1559-1565.
[13]Rodewald R,Karnovsky MJ.A self-report depression scale for reseach in the general population[J].Cell Biol,1974,60:423-433.
[14]Kestila M,Lenkkeri U,Mannikko M,et al.Polymorphisms in the nephrin gene and diabetic nephropathy in type 1 diabetic patients[J].Mol Cell,1998,1(4):575-582.
[15]Boute N,Gribouval O,Roselli S,et al.Direct effects of dexamethasone on human podocytes[J].Nat Genet,2000,24(4):349-354.
[16]Hernandez R,Teruel T,De Alvaro C,et al.Rosiglitazone ameliorates insulin resistance in brownadipocytes by impairing TNF alpha induction of p38 and p42-p44 mitogen-activated protein kinases[J].Diabetologia,2004,47(9):1615-1624.
[17]吕彩兰,戴恩来,吴建军,等.中西医结合治疗小儿原发性肾病综合征随机对照试验的Meta分析[J].华中科技大学学报:医学版,2013,42(1):87-93.
[2]Kretzschmar M,Doody J,TimokhinaI,et al.A mechanism of repression of TGFbeta/Smad signaling by oncogenic Ras[J].Genes Dev,1999,l3(7):804-816.
[3]Danziger J.Importance of low-grade albuminuria[J].Mayo Clin Proc,2008,83(7):806-812.
[4]林跃辉,嵇美霞,胡岗,等.加味参芪地黄汤辅助治疗糖尿病肾病临床观察[J].浙江中西医结合杂志,2010,20(11):679-680.
[5]白晓红,赵历军.中药肾复康对肾病患儿血清皮质醇的影响[J].辽宁中医药大学学报,2013(2):18-19.
[6]余凌,李惊子,王海燕.黄芪、当归在肾脏疾病中的应用及其机制研究进展[J].中国中西医结合杂志,2001,21(5):396-399.
[7]余凌,张峻峰,李惊子,等.黄芪当归合剂防治肾病综合征鼠进行性肾小管间质损伤[J].中华肾脏病杂志,2000,16(5):282-286.
[8]陆海英,张悦,刘煜敏,等.丹参酚酸B对肾纤维化大鼠肾组织MMP-2表达的影响[J].上海中医药大学学报,2009,23(2):55-58.
[9]王军建,胡锐.丹参酮ⅡA对阿霉素肾病大鼠肾小球nephrin和TGF-β1的表达影响[J].中国实验方剂学杂志,2011,17(19):245-251.
[10]Kim SK.Protective effect of Tanshinone IIA on the early stage of experimental diabetic nephropathy[J].Pharmaceutical Bulletin,2009,32(2):220-224.
[11]Zeisberg M,Bonner G,Maeshima Y,et al.Renal fibrosis:collagen composition and assembly regulates epithelialmesenchymal transdifferentiation[J].The American journal of pathology,2001,159(4):1313-1321.
[12]Kim uraM,AsanoM,AbeK,et al.Role of atrophic changes in proximal tubular cells in the per itubular deposition of typel collagen in a ratrenal ablation model[J].Nephrol Dial Transplant,2005,20(8):1559-1565.
[13]Rodewald R,Karnovsky MJ.A self-report depression scale for reseach in the general population[J].Cell Biol,1974,60:423-433.
[14]Kestila M,Lenkkeri U,Mannikko M,et al.Polymorphisms in the nephrin gene and diabetic nephropathy in type 1 diabetic patients[J].Mol Cell,1998,1(4):575-582.
[15]Boute N,Gribouval O,Roselli S,et al.Direct effects of dexamethasone on human podocytes[J].Nat Genet,2000,24(4):349-354.
[16]Hernandez R,Teruel T,De Alvaro C,et al.Rosiglitazone ameliorates insulin resistance in brownadipocytes by impairing TNF alpha induction of p38 and p42-p44 mitogen-activated protein kinases[J].Diabetologia,2004,47(9):1615-1624.
[17]吕彩兰,戴恩来,吴建军,等.中西医结合治疗小儿原发性肾病综合征随机对照试验的Meta分析[J].华中科技大学学报:医学版,2013,42(1):87-93.
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