Anti-perforin neutralizing antibody reduces myocardial injury in viral myocarditis

Abstract Aim To investigate the role of anti-perforin neutralizing antibody in viral myocarditis. Methods We divided 45 Balb/c mice randomly into 3 groups, a normal control group, a control group inoculated with coxsackie virus B 3, and a group inoculated with anti-perforin neutralizing antibody. The second group was inoculated with 0.15 milliliters coxsackie virus B 3 , and the third group additionally with 0.1milligrams/kilogram anti-perforin neutralizing antibody at time points of 6 hours and 3 days after infection. Histopathology was performed using haematoxylin and eosin, with apoptosis examined by the terminal transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick, end-labeling method, or Tunel. The expression of caspase-3 in myocardium was investigated by immunohistochemistry and reverse-transcription polymerase chain reaction. Results The pathologic score, myocardial viral titers, average percentages of apoptotic cardiomyocytes, expression of active caspase-3 protein and messenger ribonucleic acid in the myocardium of the mice receiving anti-PFP neutralizing antibody therapy were all significantly reduced when compared to values from the group inoculated with coxsackie virus B 3 . The rates of expression of Caspase-3 and myocardial apoptosis were positively correlated with the scores for myocardial pathology. Conclusion Our results suggest that anti- perforin neutralizing antibody can reduce the myocardial damage by blocking the perforin/granzyme pathway, and downregulating the expression of messenger ribonucleic acid and protein of Caspase-3. These approaches may offer promising novel therapeutic strategies for the clinical treatment of viral myocarditis.