1. Academic Validation
  2. Establishment of a novel myocarditis mouse model based on cyclosporine A

Establishment of a novel myocarditis mouse model based on cyclosporine A

  • Genes Genomics. 2022 Jun 6. doi: 10.1007/s13258-022-01267-4.
Tian Hao Zhao  # 1 Yi Xuan Jiang  # 1 Kai Qin Chen  # 1 Dan Qiu 1 Yan Zhe Xu 1 Chun Ye 1 Ting Ren 1 Bo Zhang 1 Bin Dai 1 Jue Hu 1 2 Jun Lu 1 Fang Liang Zhou 1 Rong Xiao 1 Fang Guo Lu 1 2 Ke Wei 3 4
Affiliations

Affiliations

  • 1 Medical College, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China.
  • 2 Hunan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China.
  • 3 Medical College, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. 004343@hnucm.edu.cn.
  • 4 Hunan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. 004343@hnucm.edu.cn.
  • # Contributed equally.
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.

Keywords

Bioinformatics; Cyclosporin A; Genes; Mouse model; Myocarditis; Signaling pathway.

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