脂质过氧化炎症损伤模型中参莲提取物对巨噬细胞功能的药效与机制探讨

尹婕; 李琦; 赵正; 杨庆; 刘思思; 李玉洁; 陈颖; 王娅杰; 翁小刚; 蔡维艳; 朱晓新

doi:10.13422/j.cnki.syfjx.20191001

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脂质过氧化炎症损伤模型中参莲提取物对巨噬细胞功能的药效与机制探讨

药理 | 更新时间：2021-02-09

- 脂质过氧化炎症损伤模型中参莲提取物对巨噬细胞功能的药效与机制探讨
- Effect of Shenlian Extract on Macrophage Function and Inflammatory Resolution in Lipid Peroxidation Inflammatory Injury Models
- 中国实验方剂学杂志 2019年25卷第10期页码：26-32
- 作者机构：
  
  1.首都医科大学　中医药学院，北京　 100069；
  2.中国中医科学院　中药研究所，北京　 100700
- 作者简介：
  
  尹婕，在读硕士，从事中药药理学研究，E-mail：yinjane@foxmail.com
  *朱晓新，研究员，博士生导师，从事中药药理学研究，E-mail：zhuxx@icmm.ac.cn
- 基金信息：
  
  国家自然科学基金项目(81573649);国家“重大新药创制”科技重大专项(2017ZX09101002-002-002;2017ZX09101002-002-008);中国中医科学院国际合作项目(GH2017-01;ZXKT17010)
- DOI：10.13422/j.cnki.syfjx.20191001
  中图分类号： R2-0; R22; R285.5
- 收稿日期：2019-01-11，
  
  网络出版日期：2019-02-11，
  
  纸质出版日期：2019-05-20
- 稿件说明：
移动端阅览
尹婕, 李琦, 赵正, 等. 脂质过氧化炎症损伤模型中参莲提取物对巨噬细胞功能的药效与机制探讨[J]. 中国实验方剂学杂志, 2019,25(10):26-32.

Jie YIN, Qi LI, Zheng ZHAO, et al. Effect of Shenlian Extract on Macrophage Function and Inflammatory Resolution in Lipid Peroxidation Inflammatory Injury Models[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(10): 26-32.
尹婕, 李琦, 赵正, 等. 脂质过氧化炎症损伤模型中参莲提取物对巨噬细胞功能的药效与机制探讨[J]. 中国实验方剂学杂志, 2019,25(10):26-32. DOI： 10.13422/j.cnki.syfjx.20191001.

Jie YIN, Qi LI, Zheng ZHAO, et al. Effect of Shenlian Extract on Macrophage Function and Inflammatory Resolution in Lipid Peroxidation Inflammatory Injury Models[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(10): 26-32. DOI： 10.13422/j.cnki.syfjx.20191001.

摘要

目的：

研究参莲(SL)提取物在脂质过氧化炎症损伤模型中，对巨噬细胞功能的作用和促进炎症消散的药效和药理机制。

方法：

利用氧化低密度脂蛋白(ox-LDL)体外诱导小鼠巨噬细胞RAW264.7细胞和人单核细胞THP-1造成脂质过氧化损伤模型，酶联免疫吸附测定(ELISA)检测不同质量浓度的SL提取物(2.5，5.0，10.0，20.0 mg·L

－1

)对巨噬细胞肿瘤坏死因子-

(TNF-

)，白细胞介素-1

(IL-1

)，单核细胞趋化蛋白-1(MCP-1)的含量；流式细胞术检测巨噬细胞泡沫化形成；transwell实验检测SL提取物对THP-1趋化功能的影响；以及用蛋白免疫印迹法(Western blot)检测诱导型一氧化氮合酶(iNOS)，炎症消散因子5脂氧合酶(ALOX5)以及对核转录因子-

B(NF-

B)信号通路中的磷酸化p65(p-p65)和磷酸化I

K(p-I

K)蛋白表达情况。

结果：

与正常组比较，ox-LDL提高M1型巨噬细胞标志物TNF-

，IL-1

，iNOS的表达(

0.01)，抑制M2型标志物IL-10的表达，促进泡沫细胞形成(

0.01)，诱导THP-1向ox-LDL趋化，提高MCP-1分泌量(

0.01)，抑制ALOX5的表达。与模型组比较，SL提取物可以降低TNF-

，IL-1

，iNOS的表达(

0.01)，提高IL-10的表达(

0.05)；能显著降低巨噬细胞吞噬脂质后泡沫化的形成(

0.01)；能降低THP-1细胞MCP-1的分泌(

0.01)，减少趋化的细胞数目(

0.01)；促进炎症消散因子ALOX5的升高(

0.05)，同时抑制p65和I

K磷酸化表达(

0.01)。

结论：

在脂质过氧化炎症损伤模型中，SL提取物具有诱导巨噬细胞M2极化，抑制巨噬细胞对ox-LDL的趋化和泡沫化的形成，提高ALOX5表达，促进炎症消散，从而改善脂质过氧化炎症损伤状态，上述功能与抑制NF-

B信号通路中p65和I

K磷酸化水平有关。

Abstract

Objective:

To study the effect of Shenlian extract (SL extract) on macrophage function and inflammatory resolution in lipid peroxidation inflammatory injury models.

Method:

The effects of different concentrations of SL extract (2.5

5.0

10.0

20.0 mg·L

-1

) on the polarization type

foam formation and chemotactic function of macrophages were detected with RAW264.7 cells induced by oxidized low-density lipoprotein(ox-LDL). Western blot was used to detect pro-inflammatory resolution factor arachidonate 5-lipoxygenase(ALOX5) and inducible inducible nitric oxide synthase(iNOS)

and phosphorylated p65 (p-p65) and phosphorylated I

K (p-I

K) in nuclear factor(NF)-

B related signaling pathways.

Result:

Compared with the control group

ox-LDL enhanced the expressions of M1 macrophage markers TNF-

IL-1

iNOS (

0.01)

inhibited the expressions of IL-10 of M2 markers

promoted foam cell formation (

0.01)

induced THP-1 chemotaxis ability

increased the content of MCP-1 (

0.01)

and inhibited the expression of ALOX5.Compared with the model group

SL extract reduced the expressions of TNF-

IL-1

and iNOS (

0.01)

increased the expression of IL-10 (

0.05)

and down-regulated the formation of foam of macrophages (

0.01). In transwell assay

SL extract obviously decreased the MCP-1 secretion and the number of chemotaxis cells (

0.01)

and promoted the increase of the inflammatory resolution factor ALOX5.The phosphorylation of p65 and I

K was inhibited significantly (

0.01).

Conclusion:

In the inflammatory damage model of lipid peroxidation

SL extract can regulate the polarization of macrophage

inhibit the chemotaxis and foaming of ox-LDL

increase the inflammatory resolution molecular expression

and improve the state of lipid peroxidation

which may be related to the inhibition of NF-

B signaling pathway.

关键词

Keywords

references

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