Study Of L-NAME Treatment On Experimental Autoimmune Myocarditis

Objective: To observe the therapeutic effect of N-nitro-L-arginine methyl ester(L-NAME), an inhibitor of NOS, on EAM in Balb/C mice and discuss the therapeuticmechanism induced by apoptosis.Methods:30male Balb/C mice were divided into normal control group, model controlgroup and experimental group randomly (n=10). Model control group and experimentalgroup were created into EAM by injection of porcine cardiac myosin subcutaneously indouble groin and axilla and pertussis toxin intraperitoneally on day0and7respectively.Model control group was intraperitoneally administered5mg/(kg·day) of physiologicalsaline after injective myosin and pertussis toxin. Experimental group wasintraperitoneally given5mg/kg/day of L-NAME on day1-21. The hearts and bloodwere processed after sacrificed on day21. Cardiac inflammation score was measured byHE staining. Heart weight/body weight (HW/BW), serum NO level, activity of iNOSand mRNA expression of iNOS in heart were measured in each group. Degree of heartapoptosis were evaluated by cardiac apoptotic index through TUNEL,immunohistochemical examination and real time PCR of Caspase-3、Caspase-8andCaspase-9.Results: Compared with normal control group, cardiac inflammation score, HW/BWlevel of NO and activity of iNOS, mRNA expression of iNOS, expression of Caspase-3,Caspase-8and Caspase-9of gene and protein level and cardiac apoptotic index weresignificantly higher (P<0.01) in model control group, and model control group washigher than experimental group (P<0.01). HW/BW was only a little elevation in modelcontrol group compared with the experiment group (P<0.05). Conclusion: Thedevelopment of EAM is related with the NO catalyzed by iNOS. L-NAME protectedcardiac myocyte via suppressing the activity of iNOS and further decreased production of NO in EAM. The mechanism may be that L-NAME alleviated myocardialinflammation through inhibited the apoptosis of cardiac myocyte.