Salvianolic acid B attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction <italic style="font-style: italic">via</italic> Nrf2-Gpx4 pathway-mediated ferroptosis

Yuanbo SUN; Yanran SONG; Shiqi WANG; Lixin SUN; Guiqin LI

doi:10.16016/j.2097-0927.202110189

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Salvianolic acid B attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction via Nrf2-Gpx4 pathway-mediated ferroptosis

Basic Medicine | 更新时间：2026-01-09

- Salvianolic acid B attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction via Nrf2-Gpx4 pathway-mediated ferroptosis
- Journal of Army Medical University Vol. 44, Issue 10, Pages: 1018-1024(2022)
- 作者机构：
  
  1.157000 黑龙江牡丹江，牡丹江医学院附属红旗医院肾脏内科
  2.157000 黑龙江牡丹江，牡丹江医学院附属红旗医院血液透析室
- 作者简介：
- 基金信息：
  
  the Youth Innovative Talent Training Program of Heilongjiang Province(UNPYSCT-2018120);the Scientific Research Project of Basic Scientific Research Expenses of Colleges and Universities in Heilongjiang Province(2019-KYYWFMY-0047);the Science and Technology Project of Red-Flag Scientific Research Fund(2018HQ-05)
- DOI：10.16016/j.2097-0927.202110189
  CLC： R285.5;R692;R693.2
- Received：29 October 2021，
  
  Revised：2022-01-27，
  
  Published：30 May 2022
- 稿件说明：
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Yuanbo SUN, Yanran SONG, Shiqi WANG, et al. Salvianolic acid B attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction via Nrf2-Gpx4 pathway-mediated ferroptosis[J]. Journal of Army Medical University, 2022, 44(10): 1018-1024.
DOI：

Yuanbo SUN, Yanran SONG, Shiqi WANG, et al. Salvianolic acid B attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction via Nrf2-Gpx4 pathway-mediated ferroptosis[J]. Journal of Army Medical University, 2022, 44(10): 1018-1024. DOI： 10.16016/j.2097-0927.202110189.

摘要

目的

基于核因子E2相关因子2(nuclear factor erythroid 2-related factor 2，Nrf2)-谷胱甘肽过氧化物酶4(glutathione peroxidase 4，Gpx4)通路介导的铁死亡途径，探究丹酚酸B对单侧输尿管梗阻(unilateral ureteral obstruction，UUO)大鼠肾脏间质纤维化(renal interstitial fibrosis，RIF)的改善作用。

方法

采用随机数字表法将40只大鼠分为假手术组、模型组、丹酚酸B组、丹酚酸B+Nrf2抑制剂组，每组10只。除假手术组外，其余各组建立UUO模型，假手术组除不结扎、剪断输尿管外，其余操作相同。丹酚酸B组灌胃100 mg·kg

-1

·d

-1

丹酚酸B，丹酚酸B+Nrf2抑制剂组在丹酚酸B组基础上腹腔注射Nrf2抑制剂ML385 30 mg·kg

-1

·d

-1

，假手术组、模型组灌胃等体积无菌生理盐水，连续9 d。HE染色和Masson染色检测肾组织形态和纤维化情况；试剂盒检测肾脏组织中Fe

、丙二醛(maleicdialdehyde，MDA)含量及超氧化物歧化酶(superoxide dismutase，SOD)活性；实时荧光定量PCR(quantitative real-time PCR，RT-qPCR)和蛋白质免疫印迹检测肾脏组织中Ⅰ型胶原(Collagen-Ⅰ，CoL-Ⅰ

)、Ⅲ型胶原(Collagen-Ⅲ，CoL-Ⅲ)、Nrf2、Gpx4的mRNA和蛋白水平。

结果

与假手术组相比，模型组肾脏组织中Fe

、MDA含量，CoL-Ⅰ、CoL-Ⅲ的mRNA和蛋白水平升高(

0.05)，血清中SOD活性降低(

0.05)，肾脏组织中Nrf2、Gpx4的mRNA和蛋白水平降低(

0.05)；与模型组相比，丹酚酸B组肾脏组织中Fe

、MDA含量，CoL-Ⅰ、CoL-Ⅲ的mRNA和蛋白水平降低(

0.05)，血清中SOD活性，肾脏组织中Nrf2、Gpx4的mRNA和蛋白水平升高(

0.05)；与丹酚酸B组相比，丹酚酸B+Nrf2抑制剂组肾脏组织中Fe

、MDA含量，CoL-Ⅰ、CoL-Ⅲ的mRNA和蛋白水平升高(

0.05)，血清中SOD活性，肾脏组织中Nrf2、Gpx4的mRNA和蛋白水平降低(

0.05)。

结论

丹酚酸B能够激活Nrf2-Gpx4通路进而抑制铁死亡实现对UUO大鼠RIF的缓解。

Abstract

Objective

To determine the improving effect of salvianolic acid B on renal interstitial fibrosis (RIF) of rats with unilateral ureteral obstruction (UUO) based on ferroptosis mediated by nuclear factor erythroid 2-related factor 2 (Nrf2)-glutathione peroxidase 4 (Gpx4) pathway.

Methods

A total of 40 rats were divided into sham operation group

model group

salvianolic acid B group

and salvianolic acid B+Nrf2 inhibitor group

with 10 rats in each group. UUO model was established in the latter 3 groups

and those of the sham operation group received the same operation except for not ligating and cutting the ureter. Salvianolic acid B of 100 mg·kg

-1

·d

-1

and Nrf2 inhibitor ML385 of 30 mg·kg

-1

·d

-1

were intragastrically administered to the corresponding groups

and sterile normal saline of equal volume was given to the sham operation group and model group

for 9 consecutive days. Hematoxylin-eosin (HE) staining and Masson staining were used to detect the morphology and fibrosis in renal tissues. The contents of Fe

maleicdialdehyde (MDA) and activity of superoxide dismutase (SOD) in renal tissues were detected with corresponding kits. Quantitative real-time P

CR (RT-qPCR) and Western blotting were used to detect the mRNA and protein levels of Collagen-Ⅰ (CoL-Ⅰ)

Collagen-Ⅲ (CoL-Ⅲ)

Nrf2

and Gpx4 in the renal tissues.

Results

Compared with the sham operation group

the contents of Fe

and MDA and the mRNA and protein levels of CoL-Ⅰ and CoL-Ⅲ in the renal tissues were increased (

0.05)

and the serum SOD activity and the mRNA and protein levels of Nrf2 were decreased (

0.05) in the model group. While the contents of Fe

and MDA and the mRNA and protein levels of CoL-Ⅰ and CoL-Ⅲ were decreased (

0.05)

and the SOD activity and the levels of Nrf2 and Gpx4 were increased (

0.05) in the salvianolic acid B group than the model group. The treatment of salvianolic acid B+Nrf2 inhibitor increased the contents of Fe

and MDA and the mRNA and protein levels of CoL-Ⅰ and CoL-Ⅲ (

0.05)

and reduced the SOD activity and the levels of Nrf2 and Gpx4 (

0.05) when compared with the salvianolic acid B group.

Conclusion

Salvianolic acid B activates the Nrf2-Gpx4 pathway and then inhibits ferroptosis to relieve RIF in UUO rats.

关键词

Keywords

references

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Salvianolic acid B attenuates renal interstitial fibrosis in rats with unilateral ureteral obstruction via Nrf2-Gpx4 pathway-mediated ferroptosis

DOI：10.16016/j.2097-0927.202110189

摘要

Abstract

关键词

Keywords

references