Effect of Fangji Fulingtang on Macrophage Polarization and Oxidative Stress in Mouse Model of Myocardial Fibrosis

SHI Lipeng; DENG Jingwei; YIN Erqian; CHEN Xin; DU Xuqin

doi:10.13422/j.cnki.syfjx.20231112

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Effect of Fangji Fulingtang on Macrophage Polarization and Oxidative Stress in Mouse Model of Myocardial Fibrosis

更新时间：2023-11-20

- Effect of Fangji Fulingtang on Macrophage Polarization and Oxidative Stress in Mouse Model of Myocardial Fibrosis
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 24, Pages: 11-18(2023)
- 作者机构：
  
  1.重庆医科大学中医药学院，重庆 400016
  2.重庆市中医院，重庆 400021
  3.重庆中医药学院，重庆 402760
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20231112
  CLC： R284;R285;R289;R287;R22;R2-031;R33;R24
- Published：20 December 2023，
  
  Published Online：31 August 2023，
  
  Received：11 May 2023，
- 稿件说明：
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石立鹏,邓静薇,尹二谦等.防己茯苓汤对心肌纤维化小鼠巨噬细胞极化和氧化应激的影响[J].中国实验方剂学杂志,2023,29(24):11-18.

SHI Lipeng,DENG Jingwei,YIN Erqian,et al.Effect of Fangji Fulingtang on Macrophage Polarization and Oxidative Stress in Mouse Model of Myocardial Fibrosis[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(24):11-18.
石立鹏,邓静薇,尹二谦等.防己茯苓汤对心肌纤维化小鼠巨噬细胞极化和氧化应激的影响[J].中国实验方剂学杂志,2023,29(24):11-18. DOI： 10.13422/j.cnki.syfjx.20231112.

SHI Lipeng,DENG Jingwei,YIN Erqian,et al.Effect of Fangji Fulingtang on Macrophage Polarization and Oxidative Stress in Mouse Model of Myocardial Fibrosis[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(24):11-18. DOI： 10.13422/j.cnki.syfjx.20231112.

摘要

目的

探讨防己茯苓汤对心肌纤维化小鼠巨噬细胞极化和氧化应激的影响。

方法

通过皮下注射异丙肾上腺素（5 mg·kg

-1

·d

-1

）构建心肌纤维化小鼠模型。将50只C57BL/6J小鼠随机分为假手术组、模型组、防己茯苓汤低、高剂量组、酒石酸美托洛尔（Meto）组，每组10只。假手术组、模型给予相应体积生理盐水灌胃，防己茯苓汤低、高剂量组分别予以防己茯苓汤低、高剂量灌胃（3.315、13.26 g·kg

-1

·d

-1

），Meto组予以酒石酸Meto灌胃（15 mg·kg

-1

·d

-1

）。2周后，观察小鼠心脏形态，计算平均细胞横截面积、心脏质量指数和心胫比，组织病理学方法观察心肌胶原沉积，酶联免疫吸附测定法（ELISA）检测血清肌酸激酶同工酶（CK-MB）、转化生长因子-

（TGF-

）、炎症因子指标［肿瘤坏死因子-

（TNF-

）、白细胞介素（IL）-1

、IL-6、IL-10］和氧化应激指标［丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）］的表达水平，免疫组织化学染色观察心肌组织CD86和CD206蛋白表达水平。

结果

与模型组比较，防己茯苓汤低、高剂量组和Meto组小鼠心脏外观形态明显减小，平均心肌细胞横截面积、心脏质量指数和心胫比显著降低（

0.01）；血清CK-MB、TGF-

水平明显降低（

0.05，

0.01）；血清促炎细胞因子TNF-

、IL-1

、IL-6表达水平明显降低（

0.05，

0.01），抗炎细胞因子IL-10明显升高（

0.05）；炎症细胞浸润、心肌损伤、胶原沉积和纤维化程度明显减轻；巨噬细胞极化标志物CD86表达水平显著降低（

0.01），CD206表达水平显著升高（

0.01）；氧化应激指标MDA表达水平显著升高（

0.01），SOD、GSH表达水平显著降低（

0.01）。

结论

防己茯苓汤可以改善异丙肾上腺素诱导的心肌纤维化，其机制可能是通过调控巨噬细胞极化和氧化应激发挥作用。

Abstract

Objective

To investigate the effects of Fangji Fulingtang on macrophage polarization and oxidative stress in the mouse model of myocardial fibrosis.

Method

The mouse model of myocardial fibrosis was established by subcutaneous injection of isoproterenol （ISO， 5 mg·kg

-1

·d

-1

）. Fifty C57BL/6J mice were randomly assigned into control （0.9% NaCl）， model （0.9% NaCl）， low- and high-dose （3.315 g·kg

-1

·d

-1

and 13.26 g·kg

-1

·d

-1

， respectively） Fangji Fulingtang （FFD-L and FFD-H， respectively）， and metoprolol tartrate （Meto， 15 mg·kg

-1

·d

-1

） groups， with 10 mice each group. After 2 weeks of treatment， the heart appearance， cardiac weight index （CWI）， heart weight （HW）/tibia length （TL） ratio， and myocardial histopathological alterations were observed. Meanwhile， the serum levels of creatine kinase-MB （CK-MB）， transforming growth factor-

（TGF-

）， tumor necrosis factor-

（TNF-

）， interleukin （IL）-1

， IL-6， IL-10， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） were measured by enzyme-linked immunosorbent assay （ELISA）. The expression levels of CD86 and CD206 were observed by immunohistochemical staining.

Result

Compared with the model group， the FFD-L， FFD-H， and Meto groups showed improved heart appearance， decreased CWI and HW/TL ratio （

0.01）， lowered serum levels of CK-MB， TGF-

， TNF-

， IL-1

， and IL-6 （

0.05，

0.01）， and elevated IL-10 level （

0.05）. Furthermore， the three groups showed reduced infiltration of inflammatory cells， myocardial injury， collagen deposition， and myocardial fibrosis， decreased CD86， SOD， and GSH （

0.01）， and increased CD206 and MDA （

0.01）.

Conclusion

Fangji Fulingtang can mitigate ISO-induced myocardial fibrosis by regulating macrophage polarization and oxidative stress.

关键词

防己茯苓汤心肌纤维化巨噬细胞极化氧化应激炎症因子

Keywords

Fangji Fulingtangmyocardial fibrosismacrophage polarizationoxidative stressinflammatory cytokine

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