Abstract:

Objective   To observe  the effects of angiotensin receptorⅡ blockers(ARB) Valsartan on the balance between  Th17 and Treg cells in chronic viral myocarditis (VMC) and explore the effects of ARB on chronic VMC and its mechanisms. Methods   BALB/c mice(n=36) were infected with CVB3 at day 1,14 and 28 to establish the chronic VMC models.The volumes of CVB3 were 0.20,0.25 and 0.30mL.The mice in the normal control group(n=6) were intraperitoneally injected with equal volumes of  normal saline without CVB3 at the same time.The survival mice infecteded with CVB3 were randomly divided into the chronic  VMC control group and the Valsartan therapy group at day 42. The mice of the Valsartan therapy group were administered with Valsartan 10mg/(kg·d) for 28 days. Blood pressure, heart weight and body weight of all the mice were  measured before execution. Lymphatic cells were extracted from the spleen and the ratio of Th17 and Treg cells was evaluated by flow cytometry. mRNA of IL-17A and foxp3 were tested by Real-time PCR.The severity of myocarditis was assessed by haematoxylin-eosin(HE) and Masson’s trichrome. Echocardiography was performed to evaluate  cardiac functions of the mice. Results   There was no significant difference in  blood pressure level among the three groups(P＞0.05). Compared with  Valsartan group and normal  control group, the ratio of heart weight in  chronic VMC group was higher，and the percentage of CD4+Th17 cell and the level of IL-17 in  chronic VMC  group were significantly up-regulated(P＜0.01)， while the pencentage of CD4+CD25+ Treg cell and cytokine of foxp3 was down-regulated (P＜0.01, P＜0.05 respectivcly). Cardiac functions of the mice in  Valsartan therapy group increased significantly. Conclusion   Th17/Treg imbalance exists in mice with chronic VMC. Valsartan can regulate Th17/Treg imbalance to ameliorate viral myocarditis and the progression of  dilated cardiomyopathy.

Key words: Chronic viral myocarditis； Th17/Treg； Angiotensin receptorⅡblockers; Valsartan; Mice