Improvement effect and mechanism of petroleum ether extract of <italic style="font-style: italic">Saposhnikovia divaricata</italic> on rheumatoid arthritis rats by regulating neutrophil extracellular traps

ZHANG Xiangyang; WEI Wei; XU Peng; LI Ning; GE Wenjing; WANG Xinyi; LIANG Ruifeng; XUE Airong

doi:10.6039/j.issn.1001-0408.2024.19.05

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Improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis rats by regulating neutrophil extracellular traps

更新时间：2024-10-11

- Improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis rats by regulating neutrophil extracellular traps
- ZHONGGUO YAOFANG Vol. 35, Issue 19, Pages: 2345-2351(2024)
- 作者机构：
  
  1.河南省中西医结合医院/河南省中医药研究院疼痛风湿科，郑州　450004
  2.河南省中西医结合医院/河南省中医药研究院中药研究所，郑州　450004
  3.河南中医药大学药学院，郑州　450046
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.19.05
  CLC： R965;R285
- Published：15 October 2024，
  
  Received：11 June 2024，
  
  Revised：21 August 2024，
- 稿件说明：
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张向阳,魏薇,徐鹏等.防风石油醚提取物调节中性粒细胞胞外诱捕网对类风湿性关节炎大鼠的改善作用及机制 ^Δ[J].中国药房,2024,35(19):2345-2351.

ZHANG Xiangyang,WEI Wei,XU Peng,et al.Improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis rats by regulating neutrophil extracellular traps[J].ZHONGGUO YAOFANG,2024,35(19):2345-2351.
张向阳,魏薇,徐鹏等.防风石油醚提取物调节中性粒细胞胞外诱捕网对类风湿性关节炎大鼠的改善作用及机制 ^Δ[J].中国药房,2024,35(19):2345-2351. DOI： 10.6039/j.issn.1001-0408.2024.19.05.

ZHANG Xiangyang,WEI Wei,XU Peng,et al.Improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis rats by regulating neutrophil extracellular traps[J].ZHONGGUO YAOFANG,2024,35(19):2345-2351. DOI： 10.6039/j.issn.1001-0408.2024.19.05.

摘要

目的

探究防风石油醚提取物通过调节中性粒细胞胞外诱捕网（NETs）对类风湿性关节炎（RA）大鼠的改善作用及机制。

方法

采用牛Ⅱ型胶原与弗氏完全佐剂建立大鼠RA模型。将造模成功的大鼠随机分为模型组和防风石油醚提取物低、中、高剂量组（55、110、220 mg/kg），另设不造模的正常组，每组10只。各组大鼠灌胃相应药液或等体积2%吐温-80溶液，每天1次，连续28 d。观察大鼠足趾肿胀度并进行关节炎指数（AI）评分，检测大鼠血清中白细胞介素1β（IL-1β）、IL-10、IL-17、肿瘤坏死因子α（TNF-α）、25-羟基维生素D

[25（OH）D

]

、髓过氧化物酶（MPO）、中性粒细胞弹性蛋白酶（NE）和NETs的水平，观察大鼠踝关节病理学形态变化，检测大鼠踝关节中瓜氨酸化组蛋白H3（CitH3）以及滑膜组织中细胞色素P450 24A1（CYP24A1）、细胞色素P450 27B1（CYP27B1）、维生素D受体（VDR）、肽基精氨酸脱亚胺酶4（PAD4）的表达水平。

结果

与模型组比较，防风石油醚提取物中、高剂量组大鼠给药后第14天至第28天的足趾肿胀度和AI评分均显著降低（

＜0.05或

＜0.01）；血清中IL-1β、IL-17、TNF-α、MPO、NE和NETs水平均显著降低，IL-10、25（OH）D

水平均显著升高（

＜0.05或

＜0.01）；踝关节间隙变宽，结构明显改善；踝关节中CitH3以及滑膜组织中CYP24A1、PAD4表达水平均显著降低，滑膜组织中CYP27B1、VDR表达水平均显著升高（

＜0.05或

＜0.01）。

结论

防风石油醚提取物可能通过调控维生素D系统，抑制NETs生成，进而改善RA症状。

Abstract

OBJECTIVE

To explore the improvement effect and mechanism of petroleum ether extract of

Saposhnikovia divaricata

on rheu

matoid arthritis （RA） rats by regulating neutrophil extracellular traps （NETs）.

METHODS

Establishment of rat RA model using bovine type Ⅱ collagen and Freund’s complete adjuvant. The model rats were randomly divided into model group and low-dose， middle-dose and high-dose groups （55， 110， 220 mg/kg） of petroleum ether extract of

S. divaricata

； the normal group without modeling was also established， with 10 rats in each group. Each group was given corresponding drugs or constant volume of 2% Tween-80 solution intragastrically， once a day， for consecutive 28 days. The toe swelling degree in rats was observed， and the arthritis index （AI） was scored. The serum levels of interleukin-1β （IL-1β）， IL-10， IL-17， tumor necrosis factor-α （TNF-α）， 25-hydroxyvitamin D

[25（OH）D

]

， myeloperoxidase （MPO）， neutrophil elastase （NE） and NETs in rats were detected. The histopathological changes in ankle joint were observed. The expression of citrullinated histone H3 （CitH3） in ankle joint as well as the expressions of cytochrome P450 24A1 （CYP24A1）， cytochrome P450 27B1 （CYP27B1）， vitamin D receptor （VDR） and peptidyl arginine deiminase 4 （PAD4） in synovium were all determined.

RESULTS

Compared with the model group， the toe swelling degree and AI score in the middle-dose and high-dose groups of petroleum ether extract of

S. divaricata

decreased significantly from day 14 to day 28 after administration （

＜0.05 or

＜0.01）. The serum levels of IL-1β， IL-17， TNF-α， MPO， NE and NETs decreased significantly， while the levels of IL-10 and 25（OH）D

increased significantly （

＜0.05 or

＜0.01）. The widened ankle joint space and the improved structure were found； the expression of CitH3 in ankle joint， and the expressions of CYP24A1 and PAD4 in synovium were down-regulated significantly， while the expressions of CYP27B1 and VDR were up-regulated sign

ificantly in synovium （

＜0.05 or

＜0.01）.

CONCLUSIONS

The petroleum ether extract of

S. divaricata

may inhibit the production of NETs and improve the symptoms of RA by regulating the vitamin D system.

关键词

类风湿性关节炎防风石油醚提取物维生素D中性粒细胞胞外诱捕网炎症因子

Keywords

Saposhnikovia divaricatapetroleum ether extractvitamin Dneutrophil extracellular trapsinflammatory factors

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Related Institution

Dept. of Obstetrics and Gynecology， Hainan Modern Women and Children’s Hospital

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Dept. of Rheumatology， Henan Province Hospital of TCM

College of Orthopedics and Traumatology， Henan University of Chinese Medicine

College of Pharmacy， Guangxi Medical University

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Improvement effect and mechanism of petroleum ether extract of Saposhnikovia divaricata on rheumatoid arthritis rats by regulating neutrophil extracellular traps

DOI：10.6039/j.issn.1001-0408.2024.19.05

摘要

Abstract

关键词

Keywords

references