| Objective:Viral myocarditis can lead to severe myocardial damage, heart failure, eventually leading to myocardial fibrosis, myocardial remodeling. Currently the pathogenesis of viral myocarditis is unknown, while treatment had poor efficacy. In recent years a number of studies have shown that mast cell and osteopontin play an important role in the development of myocarditis. Tranilast as a mast cell stabilizer, was confirmed to inhibit organ fibrosis. In this study, mice were affected with CVB3to establish viral myocarditis model to explore the possible role of tranilast in viral myocarditis fibrosis.Methods:4-week-old male BALB/C mice (n=72) were randomly divided into control group, model group and intervention group. The control group were infected with0.1ml virus-free Eagle’s medium, while model group and intervention group were infected with CVB3to establish viral myocarditis model. AND the intervention group was established by gavage of tranilast (200mg/kg/d) until the drawn day. Cardiac tissues were obtained on7,14and28days after modeling. The MC number was observed by toluidine blue staining and thionine staining. The cardiac tissues were stained with hematoxylin and eosin as well as Masson trichrome to observe the pathological changes in cardiac tissues. The mRNA and protein expression of TGF-β1and OPN in cardiac tissues was measured by RT-PCR and immunohistochemistry, then making correlation analysis for OPN mRNA and the number of MC.Result:1. Myocardial pathological changes of the7th day after modeling, the model group had myocardial necrosis, inflammatory cell infiltration, with higher pathological scores. The myocardial interstitial had a small amount collagen fibers on the14th day, while there were a large number of myocardial collagen deposition on the28th day. The CVF of this period got to the highest. Each time, the intervention group pathological changes and fibrosis were lower compared with model group. The difference was statistically significant (all P<0.05).2. The number of mast cells:each time, the number of mast cells in the intervention group was lower than the model group, while higher than the control group. The difference was statistically significant (all P<0.05).3. Expression of OPN, TGF-β1:The control group had a small amount of OPN and TGF-β1.The OPN expression of model group reached the highest level on the7th day, decreasing from the14th day, and became to the least on the28th day. The difference was statistically significant (all P<0.05). The expression of TGF-β1got higher from the7th day, being the most on the14th day, and decreased slightly on the28th day. The difference was statistically significant (all P<0.05). After the intervention of tranilast, the expression of TGF-β1and OPN was lower than the model group, while higher than the control group. The difference was statistically significant (all P<0.05).4. Correlation analysis:The number of MC and OPN expression was positively correlated. The number of MC and TGF-β1expression was positively correlated on the7th day and14th day while there was no correlation on the28th day.Conclusion:1.Tranilast can reduce myocardial fibrosis by inhibiting the expression of TGF-β1.2. Tranilast can reduce the number of mast cells, thereby reducing the expression of OPN, which plays an important role in the anti-myocardial fibrosis.Figures14, tables8, references53. |
