益气养阴、祛瘀化浊中药复方对糖尿病肾病大鼠NO、TGF-β1的影响
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摘要
目的:观察益气养阴、祛瘀化浊中药复方对糖尿病肾病大鼠NO、TGF-β1的影响,探讨其可能的作用机制。方法:采用高脂高糖饲料加腹腔注射链脲佐菌素(STZ)法建立糖尿病肾病的动物模型,实验分成正常组、中药组、阳性药组、模型组,观察各组大鼠血糖、HbA1c、24 h蛋白尿、BUN、Scr、NO、TGF-β1的变化,显微镜下观察肾脏PAI-1表达的变化。结果:模型组大鼠血糖、HbA1c、24 h蛋白尿、BUN、NO、TGF-β1表达明显高于正常组(P<0.01);中药组和阳性药组大鼠血糖、HbA1c、24 h蛋白尿、BUN、NO、TGF-β1表达明显低于模型组(P<0.01);各组大鼠血Scr的含量变化不明显,无统计学意义;光镜下模型组肾脏细胞质可见大量棕黄色颗粒表达而中药组、阳性药组上述表达有所减轻。结论:益气养阴、祛瘀化浊中药复方能有效防治糖尿病肾病,其作用机制是通过改善肾小球硬化,降低NO、TGF-β1的含量及肾脏PAI-1表达来实现的。
Objective: To observe the effects of Benefiting Qi and Nourishing Yin and Resolving Phlegem and Turbid TCM Compound Formula on diabetic nephropathy rats' NO and TGF-β1 and investigate the mechanism of its effect on diabetic nephropathy. Methods:By feeding high fat and high sugarfood and Intraperitoneal injection of STZ(45 mg/kg),we established the animal model of diabetic nephropathy. The rats were divided into Chinese medicine group(15 rats),positive medicine group(15 rats) and model group(15 rats). We observed the changes of sugar,HbA1 c,24 h proteinuria,BUN,Scr,NO and TGF-β1. Results: Sugar,HbA1 c,24 h proteinuria,BUN,NO and TGF-β1 in the kidney of the model group rats were significantly higher than those of the normal group(P<0.01). The sugar,HbA1 c,24 h proteinuria,BUN,NO and TGF-β1 in the kidney of the Chinese medicine group and positive medicine group were lower than those of the model group(P<0.01). There was no significant change in Scr content in each group. A large number of brown and yellow granules were observed in the renal cytoplasm of the model group. The above expression was alleviated in the traditional Chinese medicine group and the positive drug group. Conclusion: Benefiting Qi and Nourishing Yin and Resolving Phlegem and Turbid TCM Compound Formula can effectively prevent and treat diabetic nephropathy. The pharmacodynamic mechanism could be improving glomerular sclerosis and lowering NO,TGF-β1 and PAI-1 in the kidney.
Objective: To observe the effects of Benefiting Qi and Nourishing Yin and Resolving Phlegem and Turbid TCM Compound Formula on diabetic nephropathy rats' NO and TGF-β1 and investigate the mechanism of its effect on diabetic nephropathy. Methods:By feeding high fat and high sugarfood and Intraperitoneal injection of STZ(45 mg/kg),we established the animal model of diabetic nephropathy. The rats were divided into Chinese medicine group(15 rats),positive medicine group(15 rats) and model group(15 rats). We observed the changes of sugar,HbA1 c,24 h proteinuria,BUN,Scr,NO and TGF-β1. Results: Sugar,HbA1 c,24 h proteinuria,BUN,NO and TGF-β1 in the kidney of the model group rats were significantly higher than those of the normal group(P<0.01). The sugar,HbA1 c,24 h proteinuria,BUN,NO and TGF-β1 in the kidney of the Chinese medicine group and positive medicine group were lower than those of the model group(P<0.01). There was no significant change in Scr content in each group. A large number of brown and yellow granules were observed in the renal cytoplasm of the model group. The above expression was alleviated in the traditional Chinese medicine group and the positive drug group. Conclusion: Benefiting Qi and Nourishing Yin and Resolving Phlegem and Turbid TCM Compound Formula can effectively prevent and treat diabetic nephropathy. The pharmacodynamic mechanism could be improving glomerular sclerosis and lowering NO,TGF-β1 and PAI-1 in the kidney.
引文
[1] 唐丹丹,孟庆刚.基于复杂网络的真武汤治疗糖尿病肾病的靶点作用研究[J].中华中医药学刊,2018,36(2):365-367.
[2] 卓肖念.中西医结合治疗早期糖尿病肾病150例[J].辽宁中医杂志,2013,40(5):964-966.
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[4] 司芹芹,牛晓红,杨海卿,等.温阳益气养阴活血方治疗2型糖尿病肾病的临床疗效[J].中华中医药学刊,2018,36(3):703-705.
[5] 贾丽荣,赵印涛,王烨,等.益气养阴、祛瘀化浊中药复方对糖尿病肾病大鼠β2-MG、ET、AngⅡ的影响[J].辽宁中医杂志,2018,45(7):1494-1496.
[6] 郑晓东,冯燕,韩磊.芪蛭降糖胶囊对糖尿病肾病的疗效分析[J].中华中医药学刊,2018,36(4):994-996.
[7] 蔡艳.五味子合剂联合复方α-酮酸片对糖尿病肾病Ⅳ期尿蛋白及炎性指标的影响[J].中华中医药学刊,2018,36(7):1671-1674.
[8] 贾丽荣,王烨,岳伟光,等.糖尿病肾病研究概述[J].临床医药文献杂志,2017,4(62):12269-12272.
[9] Komers R.Paradoxesofnitricoxideinthediabetickidney[J].AmJPhysiolRenalPhysiol,2003,284(6):F1121-F1137.
[10] 刘萍,邱明才,何兰杰.2型糖尿病大鼠肾脏活性氧物质与NO关系的探讨[J].重庆医学,2012,41(23):2389-2391.
[11] Bernd H,Christian PM,Birgit H,et al.Analysis of NO synthase expression and clinical risk factors in human diabetic nephropathy[J].Nephrol Dial Transplant,2008,23(4):1346-1354.
[12] Hostetter TH.Hyperfiltration and glomerulosclerosis[J].Semin Nephrol,2003,23(2):194-199.
[13] Redko K,Anderson S.Paradoxes of nitric oxide in the diabetic kidney[J].Am J Physiol Renal Physiol,2003,284(6):1121-1137.
[14] 贾会玉,李中南,陈光亮.糖尿病肾病中转化生长因子β1/Sma和Mad相关蛋白信号通路的作用及其相关药物研究进展[J].中药药理学与毒理学杂志,2016,30(3):266-271.
[15] KRAGS,NYENGAARDJR,WOGENSENL.Comined effects of moderately elevated blood glucose and locally produced TGF-β1 on glomerular morphology and renal collagen production[J].Nephrol Dial Transplant,2007,22(9):2485 - 2496.
[16] 管鑫娟,姚伟峰,黄雌友,等.罗格列酮对早期糖尿病肾病患者血转化生长因子β1的影响[J].中国糖尿病杂志,2010,18(12):904-906.
[17] 祖丽华,秦玖刚.升清养阴汤对糖尿病肾病患者肾功能及血清TGF-β1、MMP-9、TIMP-1水平的影响[J].中华中医药学刊,2018,36(5):1189-1192.
[18] 唐伟,沈备.糖尿病患者PAI-1异常的发生机制及其治疗对策[J].国外医学生理病理科学与临床分册,2003,23(6):636-638.
[19] 李海剑,刘章锁,刘书真,等.罗格列酮对高糖条件下大鼠肾脏成纤维细胞 TGF-β1和PAI-1 mRNA表达的影响[J].郑州大学学报(医学版),2007(1):47-49.
[20] 欧三桃,陈明.金属蛋白酶组织抑制因子-1与肾间质纤维化[J].医学综述,2004(6):375-376.
[2] 卓肖念.中西医结合治疗早期糖尿病肾病150例[J].辽宁中医杂志,2013,40(5):964-966.
[3] 关欣,郑红光,张德伟.益气养阴、祛痰化浊中药复方对糖尿病肾病大鼠干预作用及其机制研究[J].中国组织工程研究与临床康复,2007,11(29):5745-5748.
[4] 司芹芹,牛晓红,杨海卿,等.温阳益气养阴活血方治疗2型糖尿病肾病的临床疗效[J].中华中医药学刊,2018,36(3):703-705.
[5] 贾丽荣,赵印涛,王烨,等.益气养阴、祛瘀化浊中药复方对糖尿病肾病大鼠β2-MG、ET、AngⅡ的影响[J].辽宁中医杂志,2018,45(7):1494-1496.
[6] 郑晓东,冯燕,韩磊.芪蛭降糖胶囊对糖尿病肾病的疗效分析[J].中华中医药学刊,2018,36(4):994-996.
[7] 蔡艳.五味子合剂联合复方α-酮酸片对糖尿病肾病Ⅳ期尿蛋白及炎性指标的影响[J].中华中医药学刊,2018,36(7):1671-1674.
[8] 贾丽荣,王烨,岳伟光,等.糖尿病肾病研究概述[J].临床医药文献杂志,2017,4(62):12269-12272.
[9] Komers R.Paradoxesofnitricoxideinthediabetickidney[J].AmJPhysiolRenalPhysiol,2003,284(6):F1121-F1137.
[10] 刘萍,邱明才,何兰杰.2型糖尿病大鼠肾脏活性氧物质与NO关系的探讨[J].重庆医学,2012,41(23):2389-2391.
[11] Bernd H,Christian PM,Birgit H,et al.Analysis of NO synthase expression and clinical risk factors in human diabetic nephropathy[J].Nephrol Dial Transplant,2008,23(4):1346-1354.
[12] Hostetter TH.Hyperfiltration and glomerulosclerosis[J].Semin Nephrol,2003,23(2):194-199.
[13] Redko K,Anderson S.Paradoxes of nitric oxide in the diabetic kidney[J].Am J Physiol Renal Physiol,2003,284(6):1121-1137.
[14] 贾会玉,李中南,陈光亮.糖尿病肾病中转化生长因子β1/Sma和Mad相关蛋白信号通路的作用及其相关药物研究进展[J].中药药理学与毒理学杂志,2016,30(3):266-271.
[15] KRAGS,NYENGAARDJR,WOGENSENL.Comined effects of moderately elevated blood glucose and locally produced TGF-β1 on glomerular morphology and renal collagen production[J].Nephrol Dial Transplant,2007,22(9):2485 - 2496.
[16] 管鑫娟,姚伟峰,黄雌友,等.罗格列酮对早期糖尿病肾病患者血转化生长因子β1的影响[J].中国糖尿病杂志,2010,18(12):904-906.
[17] 祖丽华,秦玖刚.升清养阴汤对糖尿病肾病患者肾功能及血清TGF-β1、MMP-9、TIMP-1水平的影响[J].中华中医药学刊,2018,36(5):1189-1192.
[18] 唐伟,沈备.糖尿病患者PAI-1异常的发生机制及其治疗对策[J].国外医学生理病理科学与临床分册,2003,23(6):636-638.
[19] 李海剑,刘章锁,刘书真,等.罗格列酮对高糖条件下大鼠肾脏成纤维细胞 TGF-β1和PAI-1 mRNA表达的影响[J].郑州大学学报(医学版),2007(1):47-49.
[20] 欧三桃,陈明.金属蛋白酶组织抑制因子-1与肾间质纤维化[J].医学综述,2004(6):375-376.