丹参酮ⅡA激活JAK2/STAT3信号通路减轻大鼠心肌缺血再灌注损伤

Tanshinone IIA Protecting Myocardium against Ischemia-Reperfusion Injury by Activating JAK2-STAT3 Signaling Pathway

目的:观察丹参酮IIA对心肌缺血再灌注损伤的保护作用及相关信号传导通路相关机制。方法:通过大鼠心肌细胞体外培养并建立缺血再灌注模型及体内大鼠心肌缺血再灌注模型,分别从细胞水平及动物整体水平进行研究。SD乳鼠心肌细胞体外培养建立缺血再灌注模型24 h后分别加入不同浓度丹参酮IIA通过流式细胞术检测细胞凋亡率;另外加入丹参酮IIA,AG490,丹参酮IIA及AG490,通过westernblot方法检测JAK2,PJAK2,STAT3,P-STAT3蛋白表达。40只SD大鼠分为缺血再灌注组,生理盐水对照组,丹参酮ⅡA处理组,丹参酮ⅡA+AG490组,按照TUNEL试剂盒方法检测心肌凋亡。通过westernblot方法检测JAK2,P-JAK2,STAT3,P-STAT3蛋白表达。结果:无论细胞水平还是动物整体水平,加入丹参酮IIA均能减少心肌细胞凋亡;丹参酮IIA组P-JAK2、STAT3蛋白表达较缺血再灌注组明显上升,而丹参酮ⅡA+AG490组的P-JAK2、STAT3蛋白表达较丹参酮ⅡA组明显下调。结论:丹参酮ⅡA可降低缺血再灌注引起的大鼠心肌细胞凋亡,其保护机制可能与JAK2/STAT3信号通路有关。

Objective： To study the protective effect of tanshinone IIA on myocardial ischemia- reperfution（ I / R） injury and related signaling pathway. Methods： Respectively from the cellular level and the overall level,we carried on this study through culturing rat myocardial cells in vitro then build I / R models and mading I / R models in vivo. After 24 hours when I / R models were made,different concentrations of tanshinone IIA were added,and then we tested the apoptosis rate by flow cytometry. And tanshinone IIA,AG490 and tanshinone IIA ＋ AG490 were added respectively,and then we assayed the expressions of JAK2,P- JAK2,STAT3 and P- STAT3 by Western blot. A total of 40 SD rats were divided into4 groups： I / R,tanshinone IIA,physiological saline,tanshinone IIA ＋ AG490. Apoptosis was measured by TUNEL assays.The expression of protein levels of JAK2,P- JAK2,STAT3 and P- STAT3 were analyzed by Western blot. Results： Tanshinone IIA reduced apoptosis whether cellular level or overall level. The expressions of P- JAK2 and STAT3 were increased in tanshinone IIA group compared to that in I / R group and reduced in tanshinone IIA ＋ AG490 group. Conclusion： Tanshinone IIA can reduce I / R- induced myocardial apoptosis and the protective mechanism may be related to the JAK2- STAT3 signaling pathway.