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  

Tanshinone attenuates myocardial injury via activating JAK2/STAT1 pathway in a murine model of viral myocarditis

作　　者：夏天和[1] 吴婷婷[1] 邬涛[1] 任跃[1] 王珍全[1] 吴蓉洲[1] 

机构地区：[1]温州医科大学附属第二医院育英儿童医院儿童心脏中心,325027

出　　处：《中华心血管病杂志》2015年第2期167-172,共6页Chinese Journal of Cardiology

摘　　要：目的 观察丹参酮对病毒性心肌炎小鼠心肌是否具有保护作用,并探讨其作用机制.方法 清洁级近交系Balb/c小鼠,雄性,4～6周龄,共110只.采用随机数字表法将小鼠分为5组,分别为心肌炎对照组、JAK激酶2（janus kinase 2,JAK2）抑制剂组（JAK2抑制剂组）、丹参酮ⅡA组（丹参酮组）、JAK2抑制剂加用丹参酮组（JAK2抑制剂＋丹参酮组）各25只,以及正常对照组10只.苏木精伊红（HE）染色后光镜下观察小鼠心肌组织病理学改变.免疫组织化学法、蛋白质印迹分析法检测心肌信号转导子与转录激活子1（STAT1）磷酸化表达水平.化学发光法测定小鼠血清心肌肌钙蛋白-Ⅰ（cTnI）的表达水平.将心肌病理积分与磷酸化STAT1（p-STAT1）的免疫组织化学吸光度值、血清cTnI含量作相关性分析.结果 （1）心肌病理炎症积分检测结果：JAK2抑制剂组和JAK2抑制剂＋丹参酮组小鼠心肌病理炎症积分均明显高于心肌炎对照组（3.35±0.57和3.34±0.54比2.12±0.39,P均＜0.01）,丹参酮组小鼠心肌病理炎症积分明显低于心肌炎对照组（1.40 ±0.34比2.12±0.39,P＜0.01）.（2）心肌细胞p-STAT1表达水平的检测结果：JAK2抑制剂组和JAK2抑制剂＋丹参酮组小鼠心肌p-STAT1表达水平的平吸光度值均明显低于心肌炎对照组（0.017±0.010和0.020±0.010比0.246±0.010,P均＜0.01）,与正常对照组比较差异则无统计学意义（P＞0.05）,而丹参酮组心肌p-STAT1表达水平则明显高于心肌炎对照组（0.444±0.060比0.246±0.010,P＜0.01）.（3）血清cTnI水平检测结果：心肌炎对照组、JAK2抑制剂组、丹参酮组及JAK2抑制剂＋丹参酮组小鼠血清cTnI水平均明显高于正常对照组[（0.42±0.06）、（1.17±0.25）、（0.23-±0.05）和（1.04±0.19） μg/L比（0.02±0.01） μg/L,P均＜0.01].JAK2抑制剂组和JAK2抑制剂＋丹参酮组小鼠血清cTnI水平均明显高于心肌炎对照组[（1.17±0.25）和（1.04�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

关 键 词：心肌炎 丹参酮 

分 类 号：R285.5[医药卫生—中药学]