Effect of <italic style="font-style: italic">Tripterygium wilfordii</italic> Polyglycoside<italic style="font-style: italic"> </italic>on Expression of NFAT2/COX-2 in Kidney Tissues of Rats with Diabetic Nephropathy

DUAN Fengyang; SONG Chundong; SONG Dan; DING Ying; REN Xianqing; ZHANG Xia; ZHAI Wensheng; GUO Ting; WANG Yaoxian

doi:10.13422/j.cnki.syfjx.20222445

您当前的位置：

首页 >

文章列表页 >

Effect of Tripterygium wilfordii Polyglycoside on Expression of NFAT2/COX-2 in Kidney Tissues of Rats with Diabetic Nephropathy

更新时间：2023-02-07

- Effect of Tripterygium wilfordii Polyglycoside on Expression of NFAT2/COX-2 in Kidney Tissues of Rats with Diabetic Nephropathy
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 5, Pages: 16-23(2023)
- 作者机构：
  
  1.河南中医药大学第一附属医院，郑州 450000
  2.河南中医药大学，郑州 450006
  3.北京中医药大学，北京 100029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20222445
  CLC： R2-0;R33;R289;R692
- Published：05 March 2023，
  
  Published Online：27 December 2022，
  
  Received：24 April 2022，
- 稿件说明：
扫描看全文
段凤阳,宋纯东,宋丹等.雷公藤多苷对糖尿病肾病大鼠肾组织NFAT2/COX-2表达的影响[J].中国实验方剂学杂志,2023,29(05):16-23.

DUAN Fengyang,SONG Chundong,SONG Dan,et al.Effect of Tripterygium wilfordii Polyglycosideon Expression of NFAT2/COX-2 in Kidney Tissues of Rats with Diabetic Nephropathy[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(05):16-23.
段凤阳,宋纯东,宋丹等.雷公藤多苷对糖尿病肾病大鼠肾组织NFAT2/COX-2表达的影响[J].中国实验方剂学杂志,2023,29(05):16-23. DOI： 10.13422/j.cnki.syfjx.20222445.

DUAN Fengyang,SONG Chundong,SONG Dan,et al.Effect of Tripterygium wilfordii Polyglycosideon Expression of NFAT2/COX-2 in Kidney Tissues of Rats with Diabetic Nephropathy[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(05):16-23. DOI： 10.13422/j.cnki.syfjx.20222445.

摘要

目的

基于活化T细胞核因子2（NFAT2）/环氧化酶-2（COX-2）通路探讨雷公藤多苷片（TWPT）防治糖尿病肾病（DN）肾脏损伤的可能作用机制。

方法

选取雄性清洁级SD大鼠42只，适应性喂养1周后随机分为正常组8只，造模组34只。正常组予以正常饲养，造模组采用高脂高糖饮食喂养1周后予腹腔注射链脲佐菌素（STZ）法建立DN大鼠模型，除去造模过程中死亡及失败，选取造模成功的24只随机分为模型组、缬沙坦（8.33 mg·kg

-1

·d

-1

）组、TWPT（5 mg·kg

-1

·d

-1

）组。正常组和模型组均予等体积生理盐水灌胃，6周后测量体质量，收集大鼠尿液，腹主动脉取血后处死取材，生化检测血清中的尿素氮（BUN）、肌酐（SCr）、丙氨酸氨基转移酶（ALT）、血脂血糖及尿液中的24 h尿蛋白总量（24 h UTP），苏木素-伊红（HE）及马松（Masson）染色观察肾脏病理，酶联免疫吸附测定法（ELISA）检测血清中的NFAT2、COX-2表达水平，蛋白免疫印迹法（Western blot）检测肾组织中NFAT2、COX-2蛋白表达，实时荧光定量聚合酶链式反应（Real-time PCR）检测肾组织中NFAT2、COX-2 mRNA表达。

结果

与正常组比较，模型组大鼠24 h UTP、BUN、SCr、CHO、TG、FBG及血清NFAT2、COX-2表达显著升高（

0.01），肾组织中的NFAT2、COX-2蛋白及mRNA表达显著升高（

0.01），肾脏病理示肾小球体积增大，系膜细胞轻度增生，系膜基质增宽；与模型组比较，TWPT组大鼠24 h UTP、BUN、SCr、CHO、TG、FBG均明显降低（

0.05，

0.01）；肾脏病理示肾小球形态基本正常，血清中NFAT2、COX-2表达显著降低（

0.01），肾组织中的NFAT2、COX-2 mRNA和蛋白表达显著下降（

0.01）。

结论

TWPT可减轻DN大鼠24 h UTP、保护肾功能、改善肾脏病理，其作用机制可能与下调血清及肾组织NFAT2/COX-2表达相关。

Abstract

Objective

To explore the underlying mechanism of

Tripterygium wilfordii

polyglycoside tablets

（TWPT） in the prevention and treatment of kidney injury in diabetic nephropathy （DN） through the nuclear factor of activated T-cells 2（NFAT2）/cyclooxygenase-2（COX-2） pathway.

Method

Forty-two male SD rats of SPF grade were selected and randomly divided into a normal group （

=8） and an experimental group （

=34） after one week of adaptive feeding. The rats in the normal group were fed conventionally. The DN model was established in rats of the experimental group by intraperitoneal injection of streptozotocin （STZ） following one week of feeding on a high-fat and high-glucose diet. After the death and failure cases during modeling were eliminated， the remaining 24 model rats were randomly divided into model group， valsartan （8.33 mg·kg

-1

·d

-1

） group， and TWPT （5 mg·kg

-1

·d

-1

） group. Rats in normal group and model group were given equal amounts of normal saline by gavage. After six weeks， body weight was measured and urine samples were collected. Blood samples were collected from the abdominal aorta， and then the rats were sacrificed for sampling. Biochemical indicators， such as serum blood urea nitrogen （BUN）， serum creatinine （SCr）， alanine aminotransferase （ALT）， blood lipid， blood glucose， and 24-hour urine total protein （24 h UTP）， were determined. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathology of the kidney. Enzyme-linked immunosorbent assay （ELISA） was used to detect NFAT2 and COX-2 expression levels in the serum. Western blot and Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）were adopted to detect NFAT2， COX-2 protein and mRNA expression in kidney tissues， respectively.

Result

Compared with the normal group， the model group showed elevated 24 h UTP， BUN， SCr， CHO， TG， and FBG， increased serum NFAT2 and COX-2 production and expression （

0.01）， and elevated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues （

0.01）. In addition， the pathology of the kidney showed enlarged glomeruli， mild proliferation of mesangial cells， and widened mesangial stroma. Compared with the model group， the TWPT group showed decreased 24 h UTP， BUN， SCr， CHO， TG， and FBG （

0.05，

0.01）， basically normal glomerular morphology， decreased expression of serum NFAT2 and COX-2 （

0.01）， and down-regulated protein and mRNA expression of NFAT2 and COX-2 in kidney tissues （

0.01）.

Conclusion

TWPT can alleviate 24 h UTP in DN model rats， protect renal function， and improve renal pathology， and its mechanism of action may be related to the down-regulation of NFAT2/COX-2 expression in the serum and kidney tissues.

关键词

雷公藤多苷糖尿病肾病活化T细胞核因子2（NFAT2）/环氧化酶-2（COX-2）通路实验研究

Keywords

Tripterygium wilfordii polyglycoside tabletsdiabetic nephropathynuclear factor of activated T-cells 2（NFAT2）/cyclooxygenase-2（COX-2） pathwayexperimental study

references

ZHOU H，NI W J，MENG X M，et al.MicroRNAs as regulators of immune and inflammatory responses：Potential therapeutic targets in diabetic nephropathy［J］.Front Cell Dev Biol，2021，8：1837.

WEI J，DENG X，LI Y，et al.PP2 ameliorates renal fibrosis by regulating the NF-κB/COX-2 and PPARγ/UCP2 pathway in diabetic mice［J］.Oxid Med Cell Longev，2021，doi：10.1155/2021/7394344http://dx.doi.org/10.1155/2021/7394344

GUAN Y，DAVIS L，BREYER M D，et al.Cyclooxygenase-2 contributes to diabetic nephropathy through glomerular EP4 receptor［J］.Prostaglandins Other Lipid Mediat，2022，159：106621.

ABDALLAH M S，KENNEDY C R J，STEPHAN J S，et al.Transforming growth factor-β1 and phosphatases modulate COX-2 protein expression and TAU phosphorylation in cultured immortalized podocytes［J］.Inflamm Res，2018，67（2）：191-201.

SONNEVELD R，VAN DER VLAY J，BALTISSEN M P，et al.Glucose specifically regulates TRPC6 expression in the podocyte in an AngⅡ-dependent manner［J］.Am J Pathol，2014，184（6）：1715-1726.

余剑.TRPC6/NFAT2通路在高糖诱导的肾小球系膜细胞损伤中的作用及机制探讨［D］.芜湖：皖南医学院，2021.

KIRKBY N S，CHAN M V，ZAISS A K，et al.Systematic study of constitutive cyclooxygenase-2 expression：Role of NF-κB and NFAT transcriptional pathways［J］.Proc Natl Acad Sci U S A，2016，113（2）：434-439.

WU X，HUANG Y，ZHANG Y，et al.Efficacy of tripterygium glycosides combined with ARB on diabetic nephropathy：A Meta-analysis［J］.Biosci Rep，2020，doi：10.1042/BSR20202391http://dx.doi.org/10.1042/BSR20202391.

杨超，胡智星，明瑞蕊，等.雷公藤多苷片联用甲氨蝶呤和/或来氟米特对类风湿关节炎自身抗体影响的Meta分析［J］.中国实验方剂学杂志，2023，29（5）：39-48.

王晓月，张依，陈文佳，等.从临床多组学整合调控网络探究雷公藤多苷片治疗类风湿关节炎的“效-毒”关联机制［J］.中国实验方剂学杂志，2023，29（5）：49-57.

WANG W.Different doses of Tripterygium glycosides in the treatment of diabetic nephropathy：Effects on blood lipids［J］.Kidney Blood Press Res，2018，43（3）：931-937.

黄燕如，万毅刚，孙伟，等.雷公藤多苷调节肾组织p38 MAPK信号通路改善糖尿病肾病肾小球炎症性损伤的作用和机制［J］.中国中药杂志，2014，39（21）：4102-4109.

宋纯东，侯小静，薛黎明，等.雷公藤多苷片对糖尿病肾病大鼠肾组织WT1的影响［J］.中华中医药杂志，2015，30（12）：4472-4474.

宋纯东，杨晓丽，薛黎明，等.雷公藤多苷对早期糖尿病肾病大鼠肾组织TGF-β1/p38 MAPK表达的影响［J］.中国中医基础医学杂志，2012，18（12）：1348-1350.

石光，石岩，孙晓波，等.糖尿病肾病大鼠模型制备方法与模型建立标准研究［J］.辽宁中医药大学学报，2014，16（7）：171-173.

徐叔云，卞如濂，陈修，等．药理实验方法学［M］.３版.北京：人民卫生出版社，2002．

ABDEL-LATIF R G，AHMED A F，HEEBA G H.Low-dose lixisenatide protects against early-onset nephropathy induced in diabetic rats［J］.Life Sci，2020，263：118592.

COLON S，LUAN H，LIU Y，et al.Peroxidasin and eosinophil peroxidase，but not myeloperoxidase，contribute to renal fibrosis in the murine unilateral ureteral obstruction model［J］.Am J Physiol Renal Physiol，2019，316（2）：F360-F371.

JIANG Z H，TANG Y Z，SONG H N，et al.miRNA-342 suppresses renal interstitial fibrosis in diabetic nephropathy by targeting SOX6［J］.Int J Mol Med，2020，45（1）：45-52.

李艳春，李嘉鑫，杨宇峰，等.基于“五行相生相克”理论论治糖尿病肾病［J］.中国实验方剂学杂志，2021，27（11）：240-245.

张依，王晓月，丁子禾，等.中药配伍雷公藤制剂治疗类风湿关节炎的安全性系统评价及其增效减毒网络调控机制［J］.中国实验方剂学杂志，2023，29（5）：1-8.

赵明洪，卢天明，刘莉，等.甘草减轻雷公藤多苷片所致肝损伤的作用机制［J］.中国实验方剂学杂志，2023，29（5）：24-31.

杨一博，徐颖，王璐，等.基于Notch信号通路探索菟丝子总黄酮配伍雷公藤多苷对生理小鼠卵巢生殖干细胞的作用及机制［J］.中国实验方剂学杂志，2023，29（5）：9-15.

李晶芳，韩蕊，殷宏庆，等.雷公藤治疗肾脏疾病及其不良反应的研究进展［J］.中国实验方剂学杂志，2021，27（14）：229-234.

朱子衡，万磊，刘健，等.基于Apriori关联规则和随机行走模型研究复方雷公藤制剂（新风胶囊）改善类风湿关节炎脾虚湿盛证免疫炎症的临床疗效［J］.中国实验方剂学杂志，2023，29（5）：32-38.

MA R，XU Y，JIANG W，et al.Combination of Tripterygium wilfordii Hook F and angiotensin receptor blocker synergistically reduces excretion of urinary podocytes in patients with type 2 diabetic kidney disease［J］.Biotechnol Biotechnol Equip，2015，29（1）：139-146.

FU Y，WANG C，ZHANG D，et al.Increased TRPC6 expression is associated with tubular epithelial cell proliferation and inflammation in diabetic nephropathy［J］.Mol Immunol，2018，94：75-81.

SU Y，CHEN Q，JU Y，et al.Palmitate induces human glomerular mesangial cells fibrosis through CD36-mediated transient receptor potential canonical channel 6/nuclear factor of activated T cell 2 activation［J］.Biochim Biophys Acta Mol Cell Biol Lipids，2020，1865（12）：158793.

CHENG H，FAN X，GUAN Y，et al.Distinct roles for basal and induced COX-2 in podocyte injury［J］.J Am Soc Nephrol，2009，20（9）：1953-1962.

POP-BUSUI R，KELLOGG A P，CHENG H T.Cyclooxygenase-2 pathway as a potential therapeutic target in diabetic peripheral neuropathy［J］.Curr Drug Targets，2008，9（1）：68-76.

GUAN Y，DAVIS L，BREYER M D，et al.Cyclooxygenase-2 contributes to diabetic nephropathy through glomerular EP4 receptor［J］.Prostaglandins Other Lipid Mediat，2022，159：106621.

HERNANDEZ，ASTUDILLO H，ESCALANTE B.Angiotensin Ⅱ stimulates cyclooxygenase-2 mRNA expression in renal tissue from rats with kidney failure［J］.Am J Physiol Renal Physiol，2002，282（4）：592-598.

KANG Y J，MBONYE U R，DELONG C J，et al.Regulation of intracellular cyclooxygenase levels by gene transcription and protein degradation［J］.Prog Lipid Res，2007，46（2）：108-125.

SUGIMOTO T，HANEDA M，SAWANO H，et al.Endothelin-1 induces cyclooxygenase-2 expression via nuclear factor of activated T-cell transcription factor in glomerular mesangial cells［J］.J Am Soc Nephrol，2001，12（7）：1359-1368.

WANG J，ZHANG Y，LIU L，et al.NFAT2 overexpression suppresses the malignancy of hepatocellular carcinoma through inducing Egr2 expression［J］.BMC Cancer，2020，20（1）：966.

CELIL AYDEMIR A B，MINEMATSU H，GARDNER T R，et al.Nuclear factor of activated T cells mediates fluid shear stress- and tensile strain-induced COX2 in human and murine bone cells［J］.Bone，2010，46（1）：167-175.

MENA M P，PAPIEWSKA-PAJAK I，PRZYGODZKA P，et al.NFAT2 regulates COX-2 expression and modulates the integrin repertoire in endothelial cells at the crossroads of angiogenesis and inflammation［J］.Exp Cell Res，2014，324（2）：124-136.

RU Y，LUO Y，ZHOU Y，et al.Adverse events associated with treatment of Tripterygium wilfordii Hook F：A quantitative evidence synthesis［J］.Front Pharmacol，2019，10：1250.

宋纯东，宋丹，任献青，等.雷公藤多苷片对糖尿病肾病大鼠肾组织RhoA/ROCK1表达的影响［J］.中华中医药学刊，2020，38（8）：166-169，280.

季天娇，王中元，朱云峰，等.黄芪甲苷调节PI3K/Akt/FoxO1通路抑制糖尿病大鼠肝糖异生［J］.中国实验方剂学杂志，2020，26（1）：78-86.

高歌，傅红兴，徐福远，等.雷公藤多苷在小鼠胰岛移植中的抗排斥作用［J］.医药导报，2017，36（7）：757-761.

FANG W，PENG F，YI T，et al.Biological activity and safety of Tripterygium extract prepared by sodium carbonate extraction［J］.Molecules，2012，17（9）：11113-11123.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Qidi Tangshen Prescription （QDTS） Regulate Akt1/HIF-1α/Bcl-xl Signaling Pathway to Improve Podocyte Autophagy in Diabetic Nephropathy

Effect of Modified Shengjiangsan on Renal Endoplasmic Reticulum Stress and Sirt1/PERK Pathway in Rat Model of Diabetic Nephropathy

Protective Effect and Mechanism of Mori Folium Extract on Kidney of db/db Diabetic Mice

Dendrobii Caulis Mixture-containing Serum Protects Mice from Podocyte Injury Induced by High Glucose

Related Author

GAO Fei

XIE Huidi

YU Borui

ZHOU Ying

SHI Yang

ZHANG Xianhui

LIU Hongfang

REN Meifang

Related Institution

Beijing Chaoyang District Hospital of Traditional Chinese Medicine

Dongzhimen Hospital，Beijing University of Chinese Medicine

First Medical Center of Chinese PLA General Hospital

Beijing Puren Hospital

The First Affiliated Hospital of Hebei University of Chinese Medicine

Postal code：100700
Tel：010-84076882 Email：syfjx_2010@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备11006657号-10 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

Effect of Tripterygium wilfordii Polyglycoside on Expression of NFAT2/COX-2 in Kidney Tissues of Rats with Diabetic Nephropathy

DOI：10.13422/j.cnki.syfjx.20222445

摘要

Abstract

关键词

Keywords

references