中药复方防感汤对SARS-CoV-2刺突蛋白引起的肺和结肠上皮细胞损伤的保护作用与TGF-β/Smad2/3和NF-κB通路的调节有关

黄超; 刘浩生; 梁炳君; 廖圣榕; 沈维增

doi:10.24920/004198

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中药复方防感汤对SARS-CoV-2刺突蛋白引起的肺和结肠上皮细胞损伤的保护作用与TGF-β/Smad2/3和NF-κB通路的调节有关

中国医学科学杂志（英文版） 2023年38卷第3期页码：206-217

论著 | Updated：2024-11-26

- 中药复方防感汤对SARS-CoV-2刺突蛋白引起的肺和结肠上皮细胞损伤的保护作用与TGF-β/Smad2/3和NF-κB通路的调节有关
- Affiliations：
  
  Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Shenzhen University (People’s Hospital of Shenzhen Baoan District), Shenzhen 518101, Guangdong Province, China
- Author bio：
  
  * 沈维增, E-mail：shenweizeng@163.com。
- Funds：
  
  深圳市宝安中医药发展基金会“新冠肺炎治疗和疫情防控技术研究及应用中医药专项”(2020KJCX-KTYJ-302)
- DOI：10.24920/004198
  中图分类号：
- 收稿日期：2022-12-06，
  
  录用日期：2023-6-5，
  
  网络出版日期：2023-07-03，
  
  纸质出版日期：2023-09-30
- Accepted：
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黄超, 刘浩生, 梁炳君, 等. 中药复方防感汤对SARS-CoV-2刺突蛋白引起的肺和结肠上皮细胞损伤的保护作用与TGF-β/Smad2/3和NF-κB通路的调节有关[J]. 中国医学科学杂志（英文版）, 2023,38(3):206-217.

Chao Huang, Hao-Sheng Liu, Bing-Jun Liang, et al. A Chinese Herb Prescription “Fang-gan Decoction” Protects Against Damage to Lung and Colon Epithelial Cells Caused by the SARS-CoV-2 Spike Protein by Regulating the TGF-β/Smad2/3 and NF-κB Pathways[J]. Chinese medical sciences journal, 2023, 38(3): 206-217.
黄超, 刘浩生, 梁炳君, 等. 中药复方防感汤对SARS-CoV-2刺突蛋白引起的肺和结肠上皮细胞损伤的保护作用与TGF-β/Smad2/3和NF-κB通路的调节有关[J]. 中国医学科学杂志（英文版）, 2023,38(3):206-217. DOI： 10.24920/004198.

Chao Huang, Hao-Sheng Liu, Bing-Jun Liang, et al. A Chinese Herb Prescription “Fang-gan Decoction” Protects Against Damage to Lung and Colon Epithelial Cells Caused by the SARS-CoV-2 Spike Protein by Regulating the TGF-β/Smad2/3 and NF-κB Pathways[J]. Chinese medical sciences journal, 2023, 38(3): 206-217. DOI： 10.24920/004198.

摘要

背景与目的

探讨中药复方防感汤对SARS-CoV-2刺突蛋白诱导的肺、肠损伤的体外和体内保护作用及其机制。

方法

用重组SARS-CoV-2刺突蛋白刺激BALB/c雌性小鼠和3株经防感汤预处理的细胞系。检测各组组织苏木精-伊红（HE）染色、病理评分、细胞通透性和活力以及肺、结肠ACE2表达。酶联免疫吸附测定法（ELISA）检测小鼠血清和细胞上清中炎症因子水平。蛋白质印迹法（Western blotting）检测NF-κB p65、p-NF-κB p65、p- IκB α、p-Smad2/3、TGF-β1、Caspase3、Bcl-2的表达。

结果

从病理评分以及细胞通透性和活力来看，中草药在体内和体外均对刺突蛋白诱发的肺和结肠损伤均有保护作用（

0.05）。中草药上调肺和结肠中被刺突蛋白降低的ACE2表达，显著改善刺突蛋白引起的炎症标志物的分泌紊乱，同时调节TGF-β/Smads和NF-κB通路的活性。

结论

中药复方防感汤对SARS-CoV-2刺突蛋白刺激的肺和肠组织损伤具有一定的保护作用，其机制基于对可能具有组织类型特异的NF-κB和TGF-β1/Smad通路的调控作用。

Abstract

Objective

To explore the effects and mechanisms of a traditional Chinese medicine (TCM) prescription

“

Fang-gan

Decoction” (FGD)

in protecting against SARS-CoV-2 spike protein-induced lung and intestinal injuries

in vitro

and

in vivo

Methods

Female BALB/c mice and three cell lines pretreated with FGD were stimulated with recombinant SARS-CoV-2 spike protein (spike protein). Hematoxylin-eosin (HE) staining and pathologic scoring of tissues

cell permeability and viability

and angiotensin-converting enzyme 2 (ACE2) expression in the lung and colon were detected. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the levels of inflammatory factors in serum and cell supernatant. The expression of NF-κB p65

p-NF-κB p65

p-IκBα

p-Smad2/3

TGF-β1

Caspase3

and Bcl-2 was evaluated by Western blotting.

Results

FGD protected against the damage to the lung and colon caused by the spike protein

in vivo

and

in vitro

according to the pathologic score and cell permeability and viability (

0.05). FGD up-regulated ACE2 expression

which was reduced by the spike protein in the lung and colon

significantly improved the deregulation of inflammatory markers caused by the spike protein

and regulated the activity of TGF-β/Smads and NF-κB signaling.

Conclusion

Traditional Chinese medicine has a protective effect on lung and intestinal tissue injury stimulated by the spike protein through possible regulatory functions of the NF-κB and TGF-β1/Smad pathways with tissue type specificity.

关键词

Keywords

references

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