Tanshinone attenuates myocardial injury via activating JAK2/STAT1 pathway in a murine model of viral myocarditis
10.3760/cma.j.issn.0253-3758.2015.02.021
- VernacularTitle:丹参酮通过调节JAK2/STAT1通路减轻病毒性心肌炎小鼠的心肌损伤
- Author:
Tianhe XIA
1
;
Tingting WU
;
Tao WU
;
Yue REN
;
Zhenquan WANG
;
Rongzhou WU
Author Information
1. 325027,温州医科大学附属第二医院育英儿童医院儿童心脏中心
- Keywords:
Myocarditis;
TANSHINONE
- From:
Chinese Journal of Cardiology
2015;43(2):167-172
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects of tanshinone and JAK2/STAT1 signaling pathway related mechanism in CVB3-induced myocarditis in murine.Methods A total of 110 inbred male Balb/c mice which were 4 to 6 weeks-old were randomly divided into five groups:normal control (N,n =10),myocarditis control (C,n =25),tanshinone group (T,15 mg · kg-1 · d-1,i.p.,n =25),janus kinase 2 inhibitor AG490 group (A,10 mg · kg-1 · d-1,i.p.,n =25),T + A group (H,n =25).Myocarditis was induced by 0.5 ml 10-9.51 TCID50/ml CVB3 i.p.injection for 10 days in group C,T and H.Myocardial histopathologic changes were observed and phospho-STAT1 expressions were detected by immunohistochemistry and Western blot analysis.The levels of serum cardiac troponin Ⅰ were detected with chemiluminescence immunoassay.Results (1) Compared with group C,the histopathologic scores were significantly higher in group A and H (3.35 ±0.57 and 3.34 ±0.54 vs.2.12 ±0.39,P <0.01),but lower in group T (1.40 ± 0.34 vs.2.12 ± 0.39,P < 0.01).(2) The expression of p-STAT1 protein was similar in group A and H compared to group N (P > 0.05),but was significantly lower than that in group C (0.017 ± 0.010 and 0.020 ± 0.010 vs.0.246 ± 0.010,P < 0.01).The expression of p-STAT1 protein was significantly higher in group T than in group C (P < 0.01).(3) The levels of serum cardiac troponin Ⅰ in group C,A,T and H were significantly higher than in group N ((0.42 ±0.06),(1.17 ±0.25),(0.23 ± 0.05) and (1.04 ±0.19) μg/L vs.(0.02 ±0.01) μg/L,all P <0.01).The levels of serum cardiac troponin Ⅰ were significantly higher in group A and H compared with group C ((1.17 ±0.25) and (1.04 ± 0.19)μg/L vs.(0.42 ±0.06)μg/L,P < 0.01),but were significantly lower in group T than in group C ((0.23 ±0.05) μg/L vs.(0.42 ±0.06) μg/L,P <0.01).(4) There was a negative correlation between the expression level of p-STAT1 and the histopathologic scores(y =-4.503 x + 3.371,R2 =0.738,P < 0.01),but a positive correlation between the levels of serum cardiac troponin Ⅰ and the histopathologic scores(y =1.935x + 1.165,R2 =0.766,P < 0.01).Conclusion Tanshinone could attenuate myocardial injury via upregulating the JAK2/STAT1 signaling pathway in this murine viral myocarditis model.