Rosmarinic acid protects against hypertensive nephropathy by inhibiting NADPH oxidase/ROS/NLRP3 inflammasome pathway

Ruidan CHEN; Yan ZHANG; Peili YANG; Fangtang LI; Ken CHEN; Yongjian YANG

doi:10.16016/j.1000-5404.202012049

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Rosmarinic acid protects against hypertensive nephropathy by inhibiting NADPH oxidase/ROS/NLRP3 inflammasome pathway

Basic Medicine | 更新时间：2026-01-09

- Rosmarinic acid protects against hypertensive nephropathy by inhibiting NADPH oxidase/ROS/NLRP3 inflammasome pathway
- Journal of Third Military Medical University Vol. 43, Issue 12, Pages: 1153-1161(2021)
- 作者机构：
  
  1.6100031 成都，西南交通大学临床医学院
  2.6100031 成都，西部战区总医院心血管内科
  3.400010 重庆，陆军军医大学(第三军医大学)大坪医院心血管内科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81873477)
- DOI：10.16016/j.1000-5404.202012049
  CLC： R544.1;R692;R965.1
- Received：06 December 2020，
  
  Revised：2021-01-21，
  
  Published：30 June 2021
- 稿件说明：
移动端阅览
Ruidan CHEN, Yan ZHANG, Peili YANG, et al. Rosmarinic acid protects against hypertensive nephropathy by inhibiting NADPH oxidase/ROS/NLRP3 inflammasome pathway[J]. Journal of Third Military Medical University, 2021, 43(12): 1153-1161.
DOI：

Ruidan CHEN, Yan ZHANG, Peili YANG, et al. Rosmarinic acid protects against hypertensive nephropathy by inhibiting NADPH oxidase/ROS/NLRP3 inflammasome pathway[J]. Journal of Third Military Medical University, 2021, 43(12): 1153-1161. DOI： 10.16016/j.1000-5404.202012049.

摘要

目的

探究迷迭香酸(rosmarinic acid，RA)对小鼠高血压肾病模型肾脏损伤的保护作用及其相关机制。

方法

30只6~8周龄雄性C57BL/6小鼠采用随机数字表法分为Control组，AngⅡ组(1.46 mg·kg

-1

·d

-1

)，AngⅡ+RA组(AngⅡ 1.46 mg·kg

-1

·d

-1

+RA 50 mg·kg

-1

·d

-1

)，每组10只，干预4周。检测血压、尿微量白蛋白、血肌酐及血尿素氮含量；免疫荧光检测肾组织巨噬细胞浸润情况；Masson染色检测肾组织纤维化程度；NADP

/NADPH检测试剂盒检测烟酰胺腺嘌呤二核苷酸磷酸(nicotinamide adenine dinucleotide phosphate，NADPH)氧化酶的活性；二氢乙啶超氧化物阴离子探针检测肾组织ROS水平；q-PCR及免疫印迹检测NADPH氧化酶亚基p22phox、p47phox及核苷酸结合寡聚化结构域样受体3(nucleotide-binding oligomerization domain，Leucine rich Repeat and Pyrin domain containing 3，NLRP3)、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein，ASC)、胱天蛋白酶1(caspase-1)、IL-1β、IL-18的表达水平。

结果

与Control组相比，AngⅡ组血压、尿蛋白、血肌酐、血尿素氮明显升高(

0.05)；肾脏炎症反应及纤维化程度显著增强(

0.05)。迷迭香酸干预后，显著改善血压、尿蛋白、血肌酐及血尿素氮(

0.05)；减轻肾脏炎症反应和纤维化程度(

0.05)；NADPH氧化酶亚基p22phox及p47phox表达降低、活性下降(

0.05)；肾组织ROS水平降低(

0.05)；NLRP3炎症小体相关分子NLRP3、ASC、Caspase-1及其下游IL-1β、IL-18表达下降(

0.05)。

结论

迷迭香酸通过调控NADPH氧化酶/ROS/NLRP3炎症小体通路改善高血压肾病。

Abstract

Objective

To investigate the protective effect of rosmarinic acid (RA) on hypertensive nephropathy in mice and its underlying mechanism.

Methods

Thirty male C57BL/6 mice (6~8 weeks) were randomly divided into 3 groups: control group

AngⅡ group (Angiotensin II

1.46 mg·kg

-1

·d

-1

) and AngⅡ+RA group (AngiotensinⅡ1.46 ·kg

-1

·d

-1

+ RA50 mg·kg

-1

·d

-1

)

with 10 mice in each group

and were intervened for 4 weeks. Blood pressure

urinary microalbumin

serum creatinine and blood urea nitrogen were detected. Immunofluorescence assay and Masson staining were performed respectively to observe the macrophage infiltration and the severity of renal fibrosis. In addition

the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was determined using NADP

/NADPH test kit; and the level of reactive oxygen species (ROS

) in renal tissue was tested by dihydroethidium (DHE) staining. Finally

the expression levels of NADPH oxidase subunits (p22phox

p47phox) and the following proteins were detected by RT-qPCR and western blotting: nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)

apoptosis-associated speck-like protein (ASC)

Caspase-1

IL-1β and IL-18.

Results

As compared with the control group

the indicators of blood pressure

urinary microalbumin

serum creatinine and blood urea nitrogen

as well as inflammatory reaction and fibrosis severity of kidney were all significantly increased in AngⅡgroup (

0.05). However

RA treatment significantly reversed all the above changes (

0.05). Meanwhile

RA also decreased the expression of NADPH oxidase subunits (p22phox and p47phox) and the activity of NADPH oxidase(

0.05). The level of ROS in renal tissue and the expression of NLRP3

ASC

Caspase-1

IL-1β and IL-18 were all reduced as well in AngⅡ+RA group.

Conclusion

RA may play a protective role in hypertensive nephropathy by inhibiting the activation of NADPH oxidase/ROS/NLRP3 inflammasome pathway.

关键词

Keywords

references

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