Protective Effect of Xiayuxue Tang on Renal Fibrosis Rats Based on Wnt/<italic style="font-style: italic">β</italic>-catenin and TGF-<italic style="font-style: italic">β</italic><sub>1</sub>/Smad Signal Pathway

Dan-dan WEI; Shan-shan LI; Yong-jie WANG; Ming-hao ZHANG; Xiang-hua LIU; Zhen-zhen Li; Shi-qing JIANG

doi:10.13422/j.cnki.syfjx.20210805

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Protective Effect of Xiayuxue Tang on Renal Fibrosis Rats Based on Wnt/β-catenin and TGF-β₁/Smad Signal Pathway

Classic Prescriptions | 更新时间：2021-04-20

- Protective Effect of Xiayuxue Tang on Renal Fibrosis Rats Based on Wnt/β-catenin and TGF-β₁/Smad Signal Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 27, Issue 10, Pages: 8-14(2021)
- 作者机构：
  
  1.河南中医药大学，郑州 450046
  2.河南省第三人民医院，郑州 450052
  3.郑州大学，郑州 450001
  4.河南中医药大学第一附属医院，郑州 450000
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20210805
  CLC： R2-0;R22;R285.5;R289;R33
- Received：31 January 2021，
  
  Published Online：18 March 2021，
  
  Published：20 May 2021
- 稿件说明：
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魏丹丹,李闪闪,王永杰等.下瘀血汤通过Wnt/β-catenin和TGF-β₁/Smad信号串联干预肾纤维化大鼠的机制[J].中国实验方剂学杂志,2021,27(10):8-14.

WEI Dan-dan,LI Shan-shan,WANG Yong-jie,et al.Protective Effect of Xiayuxue Tang on Renal Fibrosis Rats Based on Wnt/β-catenin and TGF-β₁/Smad Signal Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(10):8-14.
魏丹丹,李闪闪,王永杰等.下瘀血汤通过Wnt/β-catenin和TGF-β₁/Smad信号串联干预肾纤维化大鼠的机制[J].中国实验方剂学杂志,2021,27(10):8-14. DOI： 10.13422/j.cnki.syfjx.20210805.

WEI Dan-dan,LI Shan-shan,WANG Yong-jie,et al.Protective Effect of Xiayuxue Tang on Renal Fibrosis Rats Based on Wnt/β-catenin and TGF-β₁/Smad Signal Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(10):8-14. DOI： 10.13422/j.cnki.syfjx.20210805.

摘要

目的

观察下瘀血汤对腺嘌呤致肾纤维化大鼠的保护作用及其对Wnt/

-连环蛋白（

-catenin）和转化生长因子-

（TGF-

）/Smad信号通路的影响。

方法

50只SPF级SD雄性大鼠随机分为正常组，模型组，氯沙坦组（9 mg·kg

-1

），下瘀血汤低、高剂量组（2.43，4.86 g·kg

-1

），采用腺嘌呤灌胃（250 mg·kg

-1

）诱导肾纤维化大鼠模型，造模连续24 d，随后给予相应药物，给药连续30 d。采用酶联免疫吸附测定法（ELISA）测定血肌酐（SCr）和尿素氮（BUN）水平；苏木素-伊红（HE）染色观察大鼠肾脏组织病理改变情况；马松（Masson）染色观察大鼠肾脏胶原沉积情况；免疫组化法（IHC）和蛋白免疫印迹法（Western blot）测定大鼠肾脏Wnt5a，Wnt5b，

-catenin，TGF-

，Smad4，Smad7蛋白表达水平。

结果

与正常组比较，模型组大鼠SCr和BUN水平显著升高（

0.01），给予下瘀血汤干预后SCr和BUN水平显著降低（

0.01）；HE和Masson染色结果显示，与正常组比较，模型组大鼠肾间质损伤严重且肾间质胶原大量沉积，给予下瘀血汤干预后肾间质损伤减轻，胶原物质沉积减少；IHC和Western blot结果显示，与正常组比较，模型组大鼠肾脏Wnt5a，

-catenin，TGF-

表达上调（

0.01），Wnt5b，Smad7表达下调（

0.01），给予下瘀血汤干预后Wnt5a，

-catenin，TGF-

表达下调（

0.01），Wnt5b，Smad7表达上调（

0.01），且下瘀血汤低、高剂量组间差异无统计学意义。

结论

下瘀血汤对腺嘌呤致肾纤维化大鼠具有保护作用，其机制与抑制Wnt/

-catenin和TGF-

/Smad信号通路串联相关。

Abstract

Objective

To study the protective effect of Xiayuxue Tang on adenine-induced renal fibrosis model in rats and its impact on Wnt/

-catenin and transforming growth factor

（TGF-

）/Smad signal pathway.

Method

A total of 50 SPF-grade male SD rats were randomly divided into 5 groups： the normal group， the model group， the losartan group （9 mg·kg

-1

） and low and high dose （2.43，4.86 g·kg

-1

） of Xiayuxue Tang groups. The rat model of renal fibrosis was established by ig administration adenine （250 mg·kg

-1

） for 24 consecutive days. The rats were then given the corresponding drugs for 30 consecutive days. The levels of serum creatinine（SCr） and blood urea nitrogen （BUN） were measured by enzyme-linked immunosorbent assay（ELISA）. The histopathological changes of renal tissues in rats were observed by hematoxylin and eosin （HE） staining. The collagen deposition in rat renal tissue was observed by Masson staining； the protein expression levels of Wnt5a， Wnt5b，

-catenin， TGF-

， Smad4， Smad7 in renal tissue were detected respectively by immunohistochemistry（IHC） and Western blot.

Result

Compared with the normal group， the results of each experimental group showed that SCr and BUN levels significantly increased in the model group （

0.01）. SCr and BUN levels decreased significantly after the intervention with the Xiayuxue Tang （

0.01）. Compared with the normal group， HE and Masson staining results showed that rats in the model group had severe renal interstitial damage and massive deposition of renal interstitial collagen. The renal interstitial tubule injury was relieved after the intervention with the Xiayuxue Tang， and the renal interstitial collagen deposition decreased. The results of IHC and Western blot showed that compared with the normal group， the expressions of Wnt5a，

-catenin， TGF-

protein in the kidney of rats up-regulated （

0.01）， while the expressions of Wnt5b and Smad7 protein down-regulated （

0.01）. After the intervention with Xiayuxue Tang， the expressions of Wnt5a，

-catenin， TGF-

protein down-regulated （

0.01）， while the expressions of Wnt5b and Smad7 protein up-regulated（

0.01）. There was no significant difference between the low-dose and high-dose groups with Xiayuxue Tang.

Conclusion

Xiayuxue Tang has the protective effect on RIF rats induced by adenine， and its mechanism is related to the inhibition of Wnt/

-catenin and TGF-

/Smad signal pathway.

关键词

Keywords

references

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Protective Effect of Xiayuxue Tang on Renal Fibrosis Rats Based on Wnt/β-catenin and TGF-β1/Smad Signal Pathway

DOI：10.13422/j.cnki.syfjx.20210805

摘要

Abstract

关键词

Keywords

references

Protective Effect of Xiayuxue Tang on Renal Fibrosis Rats Based on Wnt/β-catenin and TGF-β₁/Smad Signal Pathway