Immune checkpoint inhibitor related myocarditis mouse model and construction method

An immune checkpoint and mouse model technology, applied in the field of medical animal models, to achieve the effects of easy promotion and application, increased success rate, and significant myocarditis manifestations

Active Publication Date: 2021-09-24
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to solve the technical problem of how to obtain a mouse model of immune checkpoint inhibitor-related myocarditis

Method used

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  • Immune checkpoint inhibitor related myocarditis mouse model and construction method
  • Immune checkpoint inhibitor related myocarditis mouse model and construction method
  • Immune checkpoint inhibitor related myocarditis mouse model and construction method

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Experimental program
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Embodiment

[0044] 1. Experimental method:

[0045]1) 30 male BALB / c mice aged 6 weeks were selected and divided into 3 groups, 10 in each group: divided into control group (control), autoimmune myocarditis group (TnI group), ICI-associated myocarditis group (TnI+ anti-PD-1 group); in addition to the control group, mice were subcutaneously injected with 0.1ml of complete Freud containing 0.25mg of mouse cardiac troponin I (TnI) peptide on day 0 and day 7, respectively. Adjuvant. The ICI-associated myocarditis group received intraperitoneal injection of PD-1 inhibitor (InVivoMab anti-mouse PD-1) at a dose of 5 mg / kg / time every 2 days from day 7 for a total of 5 times. The changes of cardiac function and molecular levels in the acute myocarditis inflammatory phase and dilated cardiomyopathy phase were detected on the 21st day and 56th day in each group of mice, respectively.

[0046] 2) The mouse heart was fixed and embedded in paraffin, and HE staining was used to evaluate the inflammato...

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Abstract

The invention relates to an immune checkpoint inhibitor related myocarditis mouse model and a construction method, and belongs to the technical field of medical animal models. The immune checkpoint inhibitor related myocarditis mouse model is constructed by subcutaneously injecting a complete Freund's adjuvant of a mouse cardiac troponin I peptide fragment into a mouse and injecting a PD-1 inhibitor into an intraperitoneal cavity of the mouse. According to the immune checkpoint inhibitor related myocarditis mouse model and the construction method, the success rate of modeling is effectively improved by determining the reasonable dosage and administration interval, the model construction method is simple and easy to implement and easy to popularize and apply, and the immune checkpoint inhibitor related myocarditis mouse model constructed by the invention provides an experimental object for the research of clinical immune checkpoint inhibitor related myocarditis pathogenesis and the screening of related myocarditis treatment drugs.

Description

technical field [0001] The invention relates to a mouse model of myocarditis associated with an immune checkpoint inhibitor and a construction method thereof, belonging to the technical field of medical animal models. Background technique [0002] Immune checkpoint inhibitors (immune checkpoint inhibitors, ICIs) are a new treatment option for tumor immunotherapy in recent years, which can kill tumor cells expressing tumor antigens by activating the immune system to achieve the purpose of anti-tumor. However, since immune checkpoints also play an important role in autoimmune tolerance, activation of the immune system by ICIs can cause widespread autoimmune responses, known as immune-related adverse effects (irAEs). The immune checkpoints associated with tumor antigens include cytotoxic T lymphocyte associated antigen-4 (CTLA-4), immune checkpoint programmed death-1 (PD-1) and Programmed cell death-ligand1 (PD-L1). Among them, cardiotoxicity caused by ICIs is one of the dead...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01K67/027
CPCA01K67/027A01K2227/105A01K2267/0368A01K2267/0387A01K2267/0375A01K2207/10
Inventor 程蕾蕾张卉沈毅辉王妍陈佳慧林瑾仪李政葛均波
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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