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Journal of Integrative Medicine ›› 2022, Vol. 20 ›› Issue (3): 274-280.doi: 10.1016/j.joim.2022.01.006

• Original Experimental Research • Previous Articles    

Tanshinone IIA prevents acute lung injury by regulating macrophage polarization

Jia-yi Zhaoa,b, Jin Puc, Jian Fana, Xin-yu Fengd, Jian-wen Xue, Rong Zhangf, Yan Shangf   

  1. a. Department of General Practice, Changhai Hospital, Naval Medical University, Shanghai 200433, China
    b. Department of General Practice, Changhai Hongkou Hospital, Shanghai 200081, China
    c. Department of Special Clinic, Changhai Hospital, Naval Medical University, Shanghai 200433, China
    d. Shanghai Institute of Biochemical and Cell biology, Chinese Academy of Sciences, Shanghai 200031, China
    e. Department of Nursing, Shidong Hospital, University of Shanghai for Science and Technology, Shanghai 200438, China 
    f. Department of Respiratory and Critical Care Medicine, Changhai Hospital, Naval Medical University, Shanghai 200433, China
  • Received:2021-05-27 Accepted:2021-11-05 Online:2022-05-09 Published:2022-02-21
  • Contact: Yan Shang, Rong Zhang E-mail:shangyan751200@163.com;31955041@qq.com

Objective

Acute lung injury (ALI) is a serious respiratory dysfunction caused by pathogen or physical invasion. The strong induced inflammation often causes death. Tanshinone IIA (Tan-IIA) is the major constituent of Salvia miltiorrhiza Bunge and has been shown to display anti-inflammatory effects. The aim of the current study was to investigate the effects of Tan-IIA on ALI.

Methods

A murine model of lipopolysaccharide (LPS)-induced ALI was used. The lungs and serum samples of mice were extracted at 3 days after treatment. ALI-induced inflammatory damages were confirmed from cytokine detections and histomorphology observations. Effects of Tan-IIA were investigated using in vivo and in vitro ALI models. Tan-IIA mechanisms were investigated by performing Western blot and flow cytometry experiments. A wound-healing assay was performed to confirm the Tan-IIA function.

Results

The cytokine storm induced by LPS treatment was detected at 3 days after LPS treatment, and alveolar epithelial damage and lymphocyte aggregation were observed. Tan-IIA treatment attenuated the LPS-induced inflammation and reduced the levels of inflammatory cytokines released not only by inhibiting neutrophils, but also by macrophage. Moreover, we found that macrophage activation and polarization after LPS treatment were abrogated after applying the Tan-IIA treatment. An in vitro assay also confirmed that including the Tan-IIA supplement increased the relative amount of the M2 subtype and decreased that of M1. Rebalanced macrophages and Tan-IIA inhibited activations of the nuclear factor κB and hypoxia-inducible factor pathways. Including Tan-IIA and macrophages also improved alveolar epithelial repair by regulating macrophage polarization. 

Conclusion

This study found that while an LPS-induced cytokine storm exacerbated ALI, including Tan-IIA could prevent ALI-induced inflammation and improve the alveolar epithelial repair, and do so by regulating macrophage polarization.

Key words: Acute lung injury, Inflammation, Cytokine storm, Tanshinone IIA, Macrophages

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