Abstract：Objective: To explore the effect of inhibiting aryl hydrocarbon receptor (AhR) on myocardial injury and cell pyroptosis in mice with coxsackievirus 3 (CVB3)-induced viral myocarditis (VMC). Methods: Totally 60 BALB/c mice were randomly divided into control group (Control), AhR inhibitor group (AhR inhibitor), model group (VMC), and VMC+AhR inhibitor group (VMC+AhR inhibitor), 15 mice in each group. Mice in VMC group and VMC+AhR inhibitor group were intraperitoneally injected with CVB3 to establish a myocarditis model. Mice in AhR inhibitor group and VMC+AhR inhibitor group were intraperitoneally injected with AhR inhibitor CH223191 (10 mg/kg). After 10 days, the cardiac ultrasound indexes of each group were detected by the high-resolution Vevo2100 small animal ultrasound imaging system; ELISA method was used to detect serum cardiac troponin l (cTnl), tumor necrosis factor-α (tumor necrosis factor-α, TNF-α), interleukin-1β (interleukin-1β, IL-1β) and IL-18; Hematoxylin-Eosin (HE) staining was used to observe the pathological changes of myocardial tissue; TUNEL staining to detect the apoptosis of myocardial tissue cells; immunohistochemical staining to determine the positive expression levels of NOD-like receptor pyrin domain containing 3 (NLRP3) and Gasdermin-D (GSDMD) in myocardial tissue; real-time fluorescent quantitative PCR and Western blot to detect expression levels on mRNA and protein of cysteinyl aspartate specific proteinase (caspase-1) , apoptosis-associated speck-like protein containing CARD (ASC), NLRP3 and GSDMD in myocardial tissue. Results: Compared with the control group, FS and EF decreased, LVIDd and LVAWd increased, the levels of cTnl, TNF-α, IL-1β and IL-18 in serum increased, the cell arrangement in myocardial tissue was disordered, accompanied by a large number of inflammatory cell infiltration, the increase of TUNEL positive rate in myocardial tissue, the NLRP3 positive expression rate and GSDMD positive expression rate. The relative expression of caspase-1, ASC, NLRP3 and GSDMD mRNA and protein were all upregulated, and the differences were statistically significant (P<0.05); Compared with the VMC group, FS and EF were elevated, LVIDd and LVAWd were reduced, serum levels of cTnl, TNF-α, IL-1β and IL-18 were decreased, myocardial histopathological damage was significantly reduced, TUNEL positive rate in myocardial tissue was decreased, meanwhile, NLRP3 positive expression rate and GSDMD positive expression rate. The relevant expression of caspase-1, ASC, NLRP3 and GSDMD mRNA and protein were downregulated, and the differences were statistically significant (P<0.05). Conclusion: Inhibition of AhR played a protective role against CVB3-induced viral myocarditis in mice anda was able to reduce myocardial tissue damage and inhibit cardiomyocyte scorching.
2022, Vol. 28 
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