Icariin Ameliorates Efferocytosis Dysfunction of Alveolar Macrophages Stimulated by Cigarette Smoke Extract via PPAR<italic style="font-style: italic">γ</italic> Signaling Pathway

ZHOU Zhexu; WU Yingshuo; CHEN Xing; WANG Xing; LIU Yang; HU Xiaobo; LIU Yaru; CHEN Yulong

doi:10.13422/j.cnki.syfjx.20230804

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Icariin Ameliorates Efferocytosis Dysfunction of Alveolar Macrophages Stimulated by Cigarette Smoke Extract via PPARγ Signaling Pathway

更新时间：2023-10-20

- Icariin Ameliorates Efferocytosis Dysfunction of Alveolar Macrophages Stimulated by Cigarette Smoke Extract via PPARγ Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 22, Pages: 47-55(2023)
- 作者机构：
  
  河南中医药大学中医药科学研究院，河南省中医方证信号传导重点实验室，河南省中医方证信号传导国际联合重点实验室，郑州 450046
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230804
  CLC： R2-0;R22;R285.5;R289;R33
- Published：20 November 2023，
  
  Published Online：29 March 2023，
  
  Received：17 November 2022，
- 稿件说明：
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周哲旭,武颖烁,陈星等.基于PPARγ信号通路探讨淫羊藿苷改善香烟烟雾提取物干预下肺泡巨噬细胞胞葬功能障碍的作用机制[J].中国实验方剂学杂志,2023,29(22):47-55.

ZHOU Zhexu,WU Yingshuo,CHEN Xing,et al.Icariin Ameliorates Efferocytosis Dysfunction of Alveolar Macrophages Stimulated by Cigarette Smoke Extract via PPARγ Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(22):47-55.
周哲旭,武颖烁,陈星等.基于PPARγ信号通路探讨淫羊藿苷改善香烟烟雾提取物干预下肺泡巨噬细胞胞葬功能障碍的作用机制[J].中国实验方剂学杂志,2023,29(22):47-55. DOI： 10.13422/j.cnki.syfjx.20230804.

ZHOU Zhexu,WU Yingshuo,CHEN Xing,et al.Icariin Ameliorates Efferocytosis Dysfunction of Alveolar Macrophages Stimulated by Cigarette Smoke Extract via PPARγ Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(22):47-55. DOI： 10.13422/j.cnki.syfjx.20230804.

摘要

目的

探讨淫羊藿苷基于过氧化物酶体增殖物激活受体

（PPAR

）信号通路改善香烟烟雾提取物（CSE）诱导下肺泡巨噬细胞胞葬功能障碍及炎症反应的作用机制。

方法

大鼠肺泡巨噬细胞NR8383分为空白组、10%香烟烟雾提取物干预后分为模型组、淫羊藿苷低、中、高浓度组（10、20、40 μmol·L

-1

）、PPAR

抑制剂组、PPAR

抑制剂联合淫羊藿苷低、中、高浓度组。Alamar Blue法检测淫羊藿苷对NR8383细胞增殖及抑制作用；流式细胞术检测NR8383细胞胞葬功能；酶联免疫吸附测定法检测肿瘤坏死因子-

（TNF-

）、转化生长因子-

（TGF-

）、乳脂球表皮生长因子8（MFG-E8）含量；蛋白免疫印迹法检测PPAR

、CD36、Ras相关C3肉毒菌毒素底物1（Rac1）蛋白的表达；实时荧光定量聚合酶链式反应（Real-time PCR）检测PPAR

、CD36、Rac1 mRNA的表达。

结果

香烟烟雾提取物建立NR8383细胞胞葬功能障碍模型，与空白组比较，模型组胞葬率降低（

0.05），TNF-

表达明显升高（

0.05），TGF-

、MFG-E8表达显著降低（

0.01），明显下调PPAR

、CD36、Rac1 mRNA及蛋白表达（

0.05，

0.01）；与模型组比较，应用淫羊藿苷后各组胞葬率明显升高（

0.05，

0.01），TNF-

表达显著降低（

0.01），TGF-

、MFG-E8表达明显增加（

0.05），上调PPAR

、CD36、Rac1蛋白及mRNA表达（

0.05，

0.01）；与淫羊藿苷单独用药组比较，PPAR

抑制剂联合淫羊藿苷组胞葬率明显降低（

0.05），PPAR

蛋白及mRNA表达明显降低（

0.05，

0.01），低浓度联合组CD36蛋白显著降低（

0.01）低浓度及中浓度联合组Rac1蛋白表达明显增加（

0.05）。

结论

淫羊藿苷改善香烟烟雾提取物导致的肺泡巨噬细胞胞葬功能障碍，其机制与调控PPAR

信号通路及细胞骨架结构重排相关。

Abstract

Objective

To investigate the mechanism of icariin in ameliorating efferocytosis dysfunction and inflammatory response of alveolar macrophages induced by cigarette smoke extract via the peroxisome proliferator-activated receptor gamma （PPAR

） signaling pathway.

Method

The untreated rat alveolar macrophages （NR8383） were taken as the blank group. The NR8383 cells treated with 10% cigarette smoke extract were divided into model， low-， medium-， and high-dose （10， 20， 40 μmol·L

-1

） icariin， PPAR

inhibitor， and PPAR

inhibitor + low-， medium-， and high-dose icariin groups. Alamar blue colorimetry was employed to examine the proliferation and toxicity of icariin on NR8383 cells. The efferocytosis rate of NR8383 cells was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of tumor necrosis factor-alpha （TNF-

）， transforming growth factor-

（TGF-

）， and milk fat globule-epidermal growth factor 8 （MFG-E8）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were employed to determine the protein and mRNA levels， respectively， of PPAR

， CD36， and RAS-related C3 botulinum toxin substrate 1 （Rac1）.

Result

The efferocytosis dysfunction model of NR8383 was established with the cigarette smoke extract. Compared with the blank control group， the model group showed decreased efferocytosis rate （

0.05）， elevated TNF-

level （

0.05）， lowered TGF-

and MFG-E8 levels （

0.01）， and down-regulated mRNA and protein levels of PPAR

， CD36， and Rac1 （

0.05，

0.01）. Compared with the model group， the treatment with icariin increased the efferocytosis rate （

0.05，

0.01）， lowered the TNF-

level （

0.01）， elevated TGF-

and MFG-E8 levels （

0.05）， and up-regulated the protein and mRNA levels of PPAR

， CD36， and Rac1 （

0.05，

0.01）. Compared with icariin alone， PPAR

inhibitor + icariin decreased the efferocytosis rate （

0.05） and down-regulated the protein and mRNA levels of PPAR

（

0.05，

0.01）. In addition， PPAR

inhibitor + low-dose icariin down-regulated the protein level of CD36 （

0.01） and PPAR

inhibitor + low-/medium-dose icariin up-regulated the protein level of Rac1 （

0.05）.

Conclusion

Icariin ameliorates the cigarette smoke extract-induced efferocytosis dysfunction of alveolar macrophage by regulating the PPAR

signaling pathway and cytoskeletal structure rearrangement.

关键词

淫羊藿苷肺泡巨噬细胞胞葬功能过氧化物酶体增殖物激活受体γ细胞骨架

Keywords

icariinalveolar macrophagesefferocytosis functionperoxisome proliferator-activated receptor gammacytoskeleton

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Icariin Ameliorates Efferocytosis Dysfunction of Alveolar Macrophages Stimulated by Cigarette Smoke Extract via PPARγ Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20230804

摘要

Abstract

关键词

Keywords

references