title: [Tanshinone attenuates myocardial injury via activating JAK2/STAT1 pathway in a murine model of viral myocarditis].
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).
  
  
  CONCLUSIONS
  Tanshinone could attenuate myocardial injury via upregulating the JAK2/STAT1 signaling pathway in this murine viral myocarditis model.
authors.affiliation: Children's Heart Center, Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Tianhe
authors.initials: T
authors.lastname: Xia
authors.affiliation: Children's Heart Center, Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Children's Heart Center, Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Children's Heart Center, Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Children's Heart Center, Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Zhenquan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Children's Heart Center, Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China. Email: wrz71@hotmail.com.
authors.forename: Rongzhou
authors.initials: R
authors.lastname: Wu
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D003384:Coxsackievirus Infections; D004195:Disease Models, Animal; D006335:Heart Injuries; D053614:Janus Kinase 2 / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000821:virology; D009206:Myocardium; D050794:STAT1 Transcription Factor / Q000187:drug effects*; D015398:Signal Transduction; D019210:Troponin I
chemical_list: D045784:Abietanes; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D019210:Troponin I; C021751:tanshinone; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2