Study on mechanism of Jianpi Bushen Lishi Recipe on treatment of hyperuricemia nephropathy by regulating positive and negative regulatory protein rebalance in TGF⁃β1/Smad signal pathway

Zhiguo ZHAO; Cheng ZHAO; Zhiqiang LIANG; Ji LI; Yuzhen WANG; Yemin CAO

doi:10.16305/j.1007-1334.2022.2003211

您当前的位置：

首页 >

文章列表页 >

Study on mechanism of Jianpi Bushen Lishi Recipe on treatment of hyperuricemia nephropathy by regulating positive and negative regulatory protein rebalance in TGF⁃β1/Smad signal pathway

更新时间：2022-07-13

- Study on mechanism of Jianpi Bushen Lishi Recipe on treatment of hyperuricemia nephropathy by regulating positive and negative regulatory protein rebalance in TGF⁃β1/Smad signal pathway
- Shanghai Journal of Traditional Chinese Medicine Vol. 56, Issue 6, Pages: 85-91(2022)
- 作者机构：
  
  1.上海中医药大学附属上海市中西医结合医院脉管病科（上海 200082）
  2.上海市中医药研究院脉管病研究所（上海 200082）
- 作者简介：
- 基金信息：
- DOI：10.16305/j.1007-1334.2022.2003211
  CLC：
扫描看全文
赵志国,赵诚,梁志强等.基于调节TGF⁃β1/Smad信号通路中正负调控蛋白再平衡探讨健脾补肾利湿方治疗高尿酸肾病的作用机制研究[J].上海中医药杂志,2022,56(06):85-91.

ZHAO Zhiguo,ZHAO Cheng,LIANG Zhiqiang,et al.Study on mechanism of Jianpi Bushen Lishi Recipe on treatment of hyperuricemia nephropathy by regulating positive and negative regulatory protein rebalance in TGF⁃β1/Smad signal pathway[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(06):85-91.
赵志国,赵诚,梁志强等.基于调节TGF⁃β1/Smad信号通路中正负调控蛋白再平衡探讨健脾补肾利湿方治疗高尿酸肾病的作用机制研究[J].上海中医药杂志,2022,56(06):85-91. DOI： 10.16305/j.1007-1334.2022.2003211.

ZHAO Zhiguo,ZHAO Cheng,LIANG Zhiqiang,et al.Study on mechanism of Jianpi Bushen Lishi Recipe on treatment of hyperuricemia nephropathy by regulating positive and negative regulatory protein rebalance in TGF⁃β1/Smad signal pathway[J].Shanghai Journal of Traditional Chinese Medicine,2022,56(06):85-91. DOI： 10.16305/j.1007-1334.2022.2003211.

摘要

目的,2,观察健脾补肾利湿方对高尿酸肾病大鼠肾组织TGF-β1/Smads信号通路的调节作用。,方法,2,建立高尿酸肾病损伤大鼠模型，随机分为模型组、别嘌醇组和中药组（健脾补肾利湿方），每组12只，另取12只SD大鼠设为空白对照组，用药8周后，采用ELISA法检测24 h尿蛋白定量（24 hUPQ）、血清尿酸（SUA）、血清肌酐（Scr），血清尿素氮（BUN）的含量；Western blot法检测大鼠肾脏组织的转化生长因子-β1（TGF-β1）、纤维粘连蛋白（FN）、Ⅳ型胶原（Col4）、Smad同源物2（Smad2）、Smad同源物3（Smad3）与Smad同源物7（Smad7）和磷酸化Smad2/3/7蛋白表达；RT-PCR法检测各组大鼠肾组织,TGF,-,β1,、,Col4,、,FN,、,Smad2/3,、,Smad7, mRNA表达。,结果,2,与模型组比较，中药组和别嘌醇组大鼠24 hUPQ、SUA、Scr和BUN表达均显著下降（,P,<,0.01），且中药组优于别嘌醇组（,P,<,0.01）；中药组大鼠肾组织TGF-β1、FN、Col4蛋白及,TGF,-,β1,、,FN,、,Col4, mRNA表达均显著下降（,P,<,0.01）；中药组大鼠肾组织Smad2/3、p-Smad2/3蛋白及,Smad2/3, mRNA表达均显著下降（,P,<,0.05）；中药组大鼠肾组织Smad7蛋白及,Smad7, mRNA表达显著上升（,P,<,0.05）。,结论,2,健脾补肾利湿方可能通过调节TGF-β1/Smad信号通路中正调控蛋白（Smad2/3）和负调控蛋白（Smad7）的再平衡，抑制TGF-β1信号通路，从而起到延缓肾纤维化的作用。

Abstract

Objective,2,To observe the regulation effect of Jianpi Bushen Lishi Recipe on TGF-β1/Smads signal pathway in renal tissue of rats with hyperuricemia nephropathy.,Methods,2,The rat model of hyperuricemia nephropathy were established， and were randomly divided into model group， allopurinol group and traditional Chinese medicine group（treated with Jianpi Bushen Lishi Recipe）， with 12 rats in each group. Another 12 SD rats were selected as the blank control group. After 8 weeks of administration， ELISA was used to detect the 24 hour urinary protein quantity （24 hUPQ） and the content of serum uric acid（SUA）， serum creatinine（Scr）and blood urea nitrogen（BUN）in plasma. Western blot was used to detect the expressions of transforming growth factor-β1 （TGF-β1）， fibronectin （FN）， collagen Ⅳ （Col4）， Smad homolog 2 （Smad2）， Smad homolog 3 （Smad3）， Smad homolog 7 （Smad7） and phosphorylated Smad2/3/7 proteins in rat renal tissue. The expression levels of ,TGF,-,β1,， ,Col4,， ,FN,，, Smad2/3, and ,Smad7, mRNA in renal tissue were determined by RT-PCR.,Results,2,Compared with model group， the expression levels of 24 hUPQ， SUA， Scr and BUN in traditional Chinese medicine group and allopurinol group were significantly decreased（,P,<,0.01），and traditional Chinese medicine group was superior than allopurinol group（,P,<,0.01）. Compared with model group， the expressions of TGF-β1， FN， Col4 protein， ,TGF,-,β1, mRNA，,Fn, mRNA and ,Col4, mRNA in renal tissue of rats in Chinese medicine group were all decreased significantly （,P,<,0.01）. And the expressions of Smad2/3，p-Smad2/3 protein and ,Smad2/3, mRNA in renal tissue of rats in traditional Chinese medicine group were decreased significantly （,P,<,0.05）. But the expressions of Smad7 protein and ,Smad7, mRNA in renal tissue of rats in traditional Chinese medicine group were increased significantly （P,<,0.05）.,Conclusion,2,Jianpi Bushen Lishi Recipe may inhibit TGF-β1 signal pathway by regulating the rebalance of positive regulatory protein （Smad2/3） and negative regulatory protein （Smad7） in the TGF-β1 signal pathway，thus delaying renal fibrosis.

关键词

高尿酸肾病健脾补肾利湿方TGF-β1/Smad信号通路作用机制

Keywords

hyperuricemia nephropathyJianpi Bushen Lishi RecipeTGF-β1/Smad signal pathwaymechanism

references

邹和群. 小管间质肾病［M］. 北京：科学技术文献出版社，2006： 159-167．

GOICOECHEA M， DE VINUESA S G， VERDALLES U， et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk［J］. Clin J Am Soc Nephrol， 2010， 5（8）： 1388-1393.

王瑾，王睿琦，奚九一，等. 奚氏痛风灵2号对慢性高尿酸血症肾病大鼠尿酸代谢的影响［J］. 包头医学院学报，2009， 25（2）： 129-131.

赵志国，曹烨民，王义成，等. 健脾补肾利湿方对高尿酸肾病模型大鼠抗炎、抗氧化作用的研究［J］. 上海中医药杂志，2017， 51（12）： 71-74．

奚九一，赵兆琳，鲁培基，等. 高尿酸血症肾病的实验动物模型研究［J］. 上海中医药杂志，2001， 35（10）： 10-12.

RUIZ-ORTEGA M， LORENZO O， REPÉREZ M， et al. Systemic infusion of angiotensin Ⅱ into normal rats activates nuclear factor-kappaB and AP-1 in the kidney： role of AT（1） and AT（2） receptors［J］. Am J Pathol， 2001， 158（5）： 1743-1756.

沈庆法. 中医临床肾病学［M］. 上海：上海科学技术文献出版社，1999： 206-211.

赵志国，曹烨民，赵诚. 奚九一辨治痛风学术经验［J］. 中医文献杂志，2020， 38（3）： 62-65.

赵兆琳，王义成，李厚铨，等. 奚氏痛风灵治疗原发性痛风与肾损害的临床观察［J］. 上海中医药杂志，2001， 35（10）： 13-14.

赵志国，曹烨民，赵诚，等. 车前地黄汤联合西药治疗慢性痛风性关节炎的临床观察［J］. 上海中医药大学学报，2019， 33（5）： 22-26.

KURIYAMA S， MARUYAMA Y， NISHIO S，et al. Serum uric acid and the incidence of CKD and hypertension［J］. Clin Exp Nephrol， 2015， 19 （6）： 1127-1134.

ORANTES NAVARRO C M， HERRERA VALDÉS R. Epidemiological characteristics of chronic kidneydisease of non-traditional causes in women of agricultural communities of El Salvador［J］. Clin Nephrol， 2015， 83（7Supl1）： 24-31.

VINDEVOGHEL L， LECHLEIDER R J， KON A， et al. SMAD3/4-dependent reanscriptional activation of the human typeⅦ collagen gene （COL7A1） promoter by transforming growth factor beta［J］. Proc Natl Acad Sci U S A， 2018， 95（25）： 14769-14774.

DENNLER S， ITOH S， VIVIEN D， et al. Direct binding of Smad3 and Smad4 to critical TGF beta-inducible elements in the promoter of human plasminogen activator inhibitor-type1 gene［J］. EMBO J， 2018， 17（11）： 3091-3100.

NAKAO A， AFRAKHTE M， MORÉ A， et al. Identification of Smad7， a TGFbeta-inducible antagonist of TGF-beta signalling［J］. Nature， 1997， 389（6651）： 631-635.

张金海，黄云剑，蔡文琴. Smad2，3，4，7蛋白在大鼠5/6肾切除肾衰模型中的定位和表达变化［J］. 第三军医大学学报，2004， 26（13）： 1141-1144.

YAMATE J， KURIBAYASHI M， KUWAMURA M， et al. Differential immunoexpressions of cytoskeletons in renal epithelial and interstitial cells in rat and canine fibrotic kidneys， and in kidney－related cell lines under fibrogenic stimuli［J］. Exp Toxicol Patho， 2018， 57 （2）： 135-147．

WANG S N， HIRSCHBERG R. BMP7 antagonizes TGF-beta-dependent fibrogenesis in mesangial cells［J］. Am J Physiol Renal Physiol， 2003， 284（5）： F1006-F1013．

中华中医药学会肾病分会. 尿酸性肾病的诊断、辨证分型及疗效评定（试行方案）［J］. 上海中医药杂志，2008， 42（1）： 23-25.

Views

237

下载量

CSCD

CNKI被引量

Alert me when the article has been cited

提交

Tools

Publicity Resources

Study on anti-inflammation and anti-oxidation effects of “Jianpi Bushen Lishi Recipe” in hyperuricemia nephropathy rats

Research progress on effective components of tripterygium wilfordii in treatment of rheumatoid arthritis

Research progress on active components and mechanism of traditional Chinese herbal medicine for antianxiety

Research progress on mechanisms of platycodin D on non-small cell lung cancer

Research progress on antitumor components and mechanism of Solanumnigrum L.

Related Author

No data

Related Institution

Department of Vascular Diseases,Shanghai Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine

Shanghai Institute of Integrated Traditional Chinese and Western Medicine for Vascular Diseases

Graduate School of Shanghai University of Traditional Chinese Medicine

Arthritis Institute of Integrated Traditional Chinese and Western Medicine， Shanghai Academy of Traditional Chinese Medicine

Department of Arthritis， Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

⁰