中华心血管病杂志
中華心血管病雜誌
중화심혈관병잡지
Chinese Journal of Cardiology
2015年
2期
167-172
,共6页
夏天和%吴婷婷%邬涛%任跃%王珍全%吴蓉洲
夏天和%吳婷婷%鄔濤%任躍%王珍全%吳蓉洲
하천화%오정정%오도%임약%왕진전%오용주
心肌炎%丹参酮
心肌炎%丹參酮
심기염%단삼동
Myocarditis%TANSHINONE
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±0.19) μg/L比(0.42 ±0.06) μg/L,P均<0.01],丹参酮组小鼠血清cTnI水平则明显低于心肌炎对照组[(0.23±0.05) μg/L比(0.42±0.06) μg/L,P<0.01].(4)相关性分析结果:p-STAT1的免疫组织化学吸光度值与心肌病理炎症积分呈负相关(R2 =0.738,P<0.01),血清cTnI含量与心肌病理炎症积分呈正相关(R2=0.766,P<0.01).结论 丹参酮可通过活化JAK2-STAT1通路,上调p-STAT1表达,从而减轻病毒性心肌炎小鼠的心肌损伤.
目的 觀察丹參酮對病毒性心肌炎小鼠心肌是否具有保護作用,併探討其作用機製.方法 清潔級近交繫Balb/c小鼠,雄性,4~6週齡,共110隻.採用隨機數字錶法將小鼠分為5組,分彆為心肌炎對照組、JAK激酶2(janus kinase 2,JAK2)抑製劑組(JAK2抑製劑組)、丹參酮ⅡA組(丹參酮組)、JAK2抑製劑加用丹參酮組(JAK2抑製劑+丹參酮組)各25隻,以及正常對照組10隻.囌木精伊紅(HE)染色後光鏡下觀察小鼠心肌組織病理學改變.免疫組織化學法、蛋白質印跡分析法檢測心肌信號轉導子與轉錄激活子1(STAT1)燐痠化錶達水平.化學髮光法測定小鼠血清心肌肌鈣蛋白-Ⅰ(cTnI)的錶達水平.將心肌病理積分與燐痠化STAT1(p-STAT1)的免疫組織化學吸光度值、血清cTnI含量作相關性分析.結果 (1)心肌病理炎癥積分檢測結果:JAK2抑製劑組和JAK2抑製劑+丹參酮組小鼠心肌病理炎癥積分均明顯高于心肌炎對照組(3.35±0.57和3.34±0.54比2.12±0.39,P均<0.01),丹參酮組小鼠心肌病理炎癥積分明顯低于心肌炎對照組(1.40 ±0.34比2.12±0.39,P<0.01).(2)心肌細胞p-STAT1錶達水平的檢測結果:JAK2抑製劑組和JAK2抑製劑+丹參酮組小鼠心肌p-STAT1錶達水平的平吸光度值均明顯低于心肌炎對照組(0.017±0.010和0.020±0.010比0.246±0.010,P均<0.01),與正常對照組比較差異則無統計學意義(P>0.05),而丹參酮組心肌p-STAT1錶達水平則明顯高于心肌炎對照組(0.444±0.060比0.246±0.010,P<0.01).(3)血清cTnI水平檢測結果:心肌炎對照組、JAK2抑製劑組、丹參酮組及JAK2抑製劑+丹參酮組小鼠血清cTnI水平均明顯高于正常對照組[(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抑製劑組和JAK2抑製劑+丹參酮組小鼠血清cTnI水平均明顯高于心肌炎對照組[(1.17±0.25)和(1.04±0.19) μg/L比(0.42 ±0.06) μg/L,P均<0.01],丹參酮組小鼠血清cTnI水平則明顯低于心肌炎對照組[(0.23±0.05) μg/L比(0.42±0.06) μg/L,P<0.01].(4)相關性分析結果:p-STAT1的免疫組織化學吸光度值與心肌病理炎癥積分呈負相關(R2 =0.738,P<0.01),血清cTnI含量與心肌病理炎癥積分呈正相關(R2=0.766,P<0.01).結論 丹參酮可通過活化JAK2-STAT1通路,上調p-STAT1錶達,從而減輕病毒性心肌炎小鼠的心肌損傷.
목적 관찰단삼동대병독성심기염소서심기시부구유보호작용,병탐토기작용궤제.방법 청길급근교계Balb/c소서,웅성,4~6주령,공110지.채용수궤수자표법장소서분위5조,분별위심기염대조조、JAK격매2(janus kinase 2,JAK2)억제제조(JAK2억제제조)、단삼동ⅡA조(단삼동조)、JAK2억제제가용단삼동조(JAK2억제제+단삼동조)각25지,이급정상대조조10지.소목정이홍(HE)염색후광경하관찰소서심기조직병이학개변.면역조직화학법、단백질인적분석법검측심기신호전도자여전록격활자1(STAT1)린산화표체수평.화학발광법측정소서혈청심기기개단백-Ⅰ(cTnI)적표체수평.장심기병리적분여린산화STAT1(p-STAT1)적면역조직화학흡광도치、혈청cTnI함량작상관성분석.결과 (1)심기병리염증적분검측결과:JAK2억제제조화JAK2억제제+단삼동조소서심기병리염증적분균명현고우심기염대조조(3.35±0.57화3.34±0.54비2.12±0.39,P균<0.01),단삼동조소서심기병리염증적분명현저우심기염대조조(1.40 ±0.34비2.12±0.39,P<0.01).(2)심기세포p-STAT1표체수평적검측결과:JAK2억제제조화JAK2억제제+단삼동조소서심기p-STAT1표체수평적평흡광도치균명현저우심기염대조조(0.017±0.010화0.020±0.010비0.246±0.010,P균<0.01),여정상대조조비교차이칙무통계학의의(P>0.05),이단삼동조심기p-STAT1표체수평칙명현고우심기염대조조(0.444±0.060비0.246±0.010,P<0.01).(3)혈청cTnI수평검측결과:심기염대조조、JAK2억제제조、단삼동조급JAK2억제제+단삼동조소서혈청cTnI수평균명현고우정상대조조[(0.42±0.06)、(1.17±0.25)、(0.23-±0.05)화(1.04±0.19) μg/L비(0.02±0.01) μg/L,P균<0.01].JAK2억제제조화JAK2억제제+단삼동조소서혈청cTnI수평균명현고우심기염대조조[(1.17±0.25)화(1.04±0.19) μg/L비(0.42 ±0.06) μg/L,P균<0.01],단삼동조소서혈청cTnI수평칙명현저우심기염대조조[(0.23±0.05) μg/L비(0.42±0.06) μg/L,P<0.01].(4)상관성분석결과:p-STAT1적면역조직화학흡광도치여심기병리염증적분정부상관(R2 =0.738,P<0.01),혈청cTnI함량여심기병리염증적분정정상관(R2=0.766,P<0.01).결론 단삼동가통과활화JAK2-STAT1통로,상조p-STAT1표체,종이감경병독성심기염소서적심기손상.
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.