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Establishment of a novel myocarditis mouse model based on cyclosporine A

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Abstract

Background

Myocarditis is a myocardial injury that can easily cause adolescent death. Traditional research models of animal invasion with viral components, lipopolysaccharide (LPS) or porcine myocardial myosin, among others, have the shortcomings of potential biological safety hazards and high animal mortality.

Objective

To explore the construction of a novel myocarditis model with cyclosporine A and the potential genes and pathways associated with it.

Methods

BALB/c mice were used in this study, and cyclosporin A and LPS were injected into the peritoneal cavity of mice. The successful establishment of the model was assessed by detecting serum myocardial injury markers and inflammatory factors levels, HE, IHC staining, and RT-qPCR methods. Key genes were obtained using the GSE35182 dataset from the GEO database and validated with the RT-qPCR method.

Results

We found that a large number of inflammatory cells infiltrated the myocardium of mice in each group of Cyclosporin A constructed model, while the expression of inflammatory factor indicators was increased, and this model has the characteristics of high degree of local inflammation in myocardial tissue, low mortality, and safe and non-toxic treatment. Using GSE35182 data, we selected 18 Hub genes and validated Hub genes in myocardial tissue with RT-qPCR and found that multiple signaling pathways such as Toll-likereceptor signaling pathway(TLRs), Rap1 signal pathway(Rap1), and Chemokine signaling pathway may be involved in the development of myocarditis.

Conclusion

Cyclosporin A can construct a new myocarditis model, and TLRs, Chemokines and Rap1 signaling pathways may be the core pathways of myocarditis.

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Acknowledgements

This research was supported by grants from the National Natural Science Foundation of China (82074250) , the Natural Science Foundation of Hunan Province (2021JJ30508 and 2020JJ4063) , the Hunan Province Chinese Medicine Research Program Project (2021055) , Changsha Outstanding Innovative Youth Training Program (kq2009070) , Basic Medicine (1), Key Discipline of Hunan University of Traditional Chinese Medicine, Excellent Teaching Team for Postgraduates in Hunan Province (Teaching Team for Postgraduates in Basic Medicine, 118) and Hunan University Student Innovation and Entrepreneurship Training Program (S202110541048)

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Author notes

  1. Tian Hao Zhao, Yi Xuan Jiang and Kai Qin Chen have contributed equally to this paper.

Authors and Affiliations

  1. Medical College, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China

    Tian Hao Zhao, Yi Xuan Jiang, Kai Qin Chen, Dan Qiu, Yan Zhe Xu, Chun Ye, Ting Ren, Bo Zhang, Bin Dai, Jue Hu, Jun Lu, Fang Liang Zhou, Rong Xiao, Fang Guo Lu & Ke Wei

  2. Hunan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China

    Jue Hu, Fang Guo Lu & Ke Wei

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  1. Tian Hao Zhao
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Correspondence to Ke Wei.

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The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Experimental Animals of Hunan University of Chinese Medicine, China (LL2020120202, 1 December 2020).

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13258_2022_1267_MOESM1_ESM.tif

Supplementary Information All of the datasets analyzed were acquired from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/gds). We declare that the data and materials in this study will be provided free of charge to scientists for noncommercial purposes (TIF 32104 KB)

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Zhao, T.H., Jiang, Y.X., Chen, K.Q. et al. Establishment of a novel myocarditis mouse model based on cyclosporine A. Genes Genom 44, 1593–1605 (2022). https://doi.org/10.1007/s13258-022-01267-4

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