清热活血解毒方对银屑病发病中神经生长因子的干预研究

Jun-hui WANG; Ying-juan JIANG; Min LI; Ning WANG; Bing-nan CUI; Wa-li LIU

doi:10.1007/s11655-021-3493-4

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清热活血解毒方对银屑病发病中神经生长因子的干预研究

Original Article | Updated：2022-03-18

- 清热活血解毒方对银屑病发病中神经生长因子的干预研究
- Effects of Qingre Huoxue Jiedu Formula on Nerve Growth Factor-Induced Psoriasis
- Chinese Journal of Integrative Medicine 2022年28卷第3期页码：236-242
- Affiliations：
  
  1.Dermatology Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing (100053),China
  2.Dermatology Department, Dongfang Hospital,Beijing University of Chinese Medicine, Beijing (100078), China
  3.Laboratory of Molecular Biology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing (100053), China
- Author bio：
  
  Prof. CUI Bing-nan, E-mail: cuibn_doc@yeah.net
- Funds：
  
  the National Natural Science Foundation of China(81403398);China Academy of Chinese Medical Sciences Innovation Fund(CI2021A02314);the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ13-YQ-021)
- DOI：10.1007/s11655-021-3493-4
  中图分类号：
- 纸质出版日期：2022-03-01，
  
  网络出版日期：2021-12-12，
  
  录用日期：2020-02-01
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Jun-hui WANG, Ying-juan JIANG, Min LI, 等. 清热活血解毒方对银屑病发病中神经生长因子的干预研究[J]. Chinese Journal of Integrative Medicine, 2022,28(3):236-242.

Jun-hui WANG, Ying-juan JIANG, Min LI, et al. Effects of Qingre Huoxue Jiedu Formula on Nerve Growth Factor-Induced Psoriasis[J]. Chinese Journal of Integrative Medicine, 2022,28(3):236-242.
Jun-hui WANG, Ying-juan JIANG, Min LI, 等. 清热活血解毒方对银屑病发病中神经生长因子的干预研究[J]. Chinese Journal of Integrative Medicine, 2022,28(3):236-242. DOI： 10.1007/s11655-021-3493-4.

Jun-hui WANG, Ying-juan JIANG, Min LI, et al. Effects of Qingre Huoxue Jiedu Formula on Nerve Growth Factor-Induced Psoriasis[J]. Chinese Journal of Integrative Medicine, 2022,28(3):236-242. DOI： 10.1007/s11655-021-3493-4.

摘要

目的:

神经生长因子(NGF)作为神经内分泌-细胞免疫网络的主要节点

该递质及其受体系统参与了银屑病皮损形成的早期过程

在银屑病的发病中起到了至关重要的作用. 本研究目的在于阐明神经生长因子对角质形成细胞、T细胞的诱导增殖作用及活血解毒方的4种有效单体: 紫草素、丹皮酚、落新妇苷和熊果酸的可能干预机制.

方法:

培养Hacat细胞、Jurkat cell细胞

添加NGF溶液(NGF+DMEM

100ng/mL)对两种细胞进行诱导增殖24小时

作为诱导组; 此外另加入NGF受体阻滞剂NTRK1 ((K252a+DEME

300 nmol/L) 1小时作为对照. 以上各组分别使用清热活血解毒方中4种有效单体: 紫草素、丹皮酚、落新妇苷和熊果酸进行干预. 通过流式细胞术分析和CCK8测定来检测细胞凋亡和增殖

实时定量荧光检测 (RT-PCR) 评估凋亡基因Bax、Bcl-xl

神经生长因子受体(NGFR)mRNA表达水平

同时进行蛋白质印迹分析 (Western blot analysis) .

结果:

(1) 清热活血解毒有效单体干预组与NGF诱导组相比

细胞凋亡增加

细胞增殖抑制 (<0.05) . 且同时加入NTRK1及清热活血解毒有效单体的干预组在细胞凋亡、细胞增殖抑制作用方面更显著

特别是熊果酸组表现更为明显

(2) 清热活血解毒有效单体干预组Bax、Bcl-xl蛋白表达水平高于其他组(<0.05). 且同时加入NTRK1及清热活血解毒有效单体显着增加了细胞Bax、Bcl-xl和NGFR的蛋白质表达水平

尤其是紫草素组表现更为明显.

结论:

清热活血解毒方治疗银屑病的作用机制可能与影响细胞凋亡增殖

并上调Bax、Bcl-xl和NGFR的表达水平相关

但具体机制仍需要进一步研究.

Abstract

Objective:

To elucidate the mechanisms of 4 effective components from a Chinese medicine formula

namely Qingre Huoxue Jiedu Formula (QHJ heat- and toxin-clearing and blood-activating formula)

in the treatment of nerve growth factor (NGF)-induced psoriasis.

Methods:

Keratinocyte proliferation and T cell proliferation models were developed using NGF. An NGF solution (NGF+DMEM

100 ng/mL) was added to all induced groups and treated groups and were cultured for 24 h

while a solution with NTRK1 antagonist (K252a+DEME

300 nmol/L) was added and cultured for 1 h. The models were used to evaluate the effects of the treatment with each of the 4 components of QHJ

namely shikonin

paeonol

astilbin and ursolic acid. Cell apoptosis and proliferation were measured by flow cytometry analysis and CCK8 assay

respectively. The mRNA expression levels of Bax

Bcl-xl

and NGF receptor (NGFR) were assessed by quantitative real-time PCR (qRT-PCR) and Western blot analysis

respectively.

Results:

(1) All QHJ-treated groups showed significantly increased cell apoptosis and inhibition of cell proliferation compared with the NGF-induced groups (

0.05). In addition

treatment with QHJ plus NTRK1 significantly enhanced cell apoptosis and inhibition of cell proliferation compared with cells treated with QHJ only (

0.05)

particularly in cells treated with ursolic acid. (2) QHJ-treated groups showed higher protein expression levels of Bax

Bcl-xl compared with other groups (

0.05). Additionally

treatment with QHJ plus NTRK1 significantly increased the protein expression levels of Bax

Bcl-xl and NGFR compared with those treated with QHJ only (all

0.05)

especially in those treated with shikonin.

Conclusion:

The action mechanism of QHJ on psoriasis might be through enhancing cell apoptosis and inhibition of cell proliferation

and upregulating the expression level of Bax

Bcl-xl and NGFR.

关键词

Keywords

psoriasisinflammatory dermatosisnerve growth factorkeratinocyteChinese medicine formula

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