CAJ | 학술논문

目的观察活性氧簇(ROS)在缺血后处理抗心肌细胞凋亡机制中的作用,探讨ROS在缺血后处理机制中对酪氨酸激酶2(JAK2)-信号传导与转录激活因子3(STAT3)通路的影响.方法将健康雄性成年Wistar大鼠(体质量240～280g)随机分为假手术组、缺血再灌注损伤组、缺血后处理组及缺血后处理+N-(2-巯基丙酰基)-甘氨酸(MPG)组.TUNEL法检测心肌细胞凋亡比率;免疫组织化学法检测bcl-2及bcl-xL蛋白水平;Western blot法检测磷酸化STAT3水平.结果与缺血再灌注损伤组比较,缺血后处理显著上调再灌注后bcl-2(42.4±5.6比8.6±2.4,P＜0.05)及bcl-xL(19.9±3.2比9.6±2.5,P＜0.05)水平,抑制再灌注后心肌细胞凋亡(37.8±4.0比56.9±6.0,P＜0.05).缺血后处理+MPG组较缺血后处理组bcl-2(10.5±2.1比42.4±5.6,P＜0.05)及bcl-xL(9.9±2.3比19.9±3.2,P＜0.05)水平显著降低,心肌细胞凋亡比率显著升高(55.7±7.7比37.8±4.0,P＜0.05).缺血后处理显著上调再灌注后磷酸化STAT3水平(0.27±0.02比0.43±0.08,P＜0.05).缺血后处理前使用MPG显著降低STAT3磷酸化水平(0.27±0.04比0.43±0.08,P＜0.05),抑制JAK2-STAT3通路活性.结论 ROS在缺血后处理抗心肌细胞凋亡作用中具有重要作用.缺血后处理可能通过氧化还原信号激活JAK2-STAT3通路,并进一步调节STAT3下游bcl家族抗凋亡蛋白表达水平而发挥抗凋亡作用.
목적 관찰활성양족(ROS)재결혈후처리항심기세포조망궤제중적작용,탐토ROS재결혈후처리궤제중대락안산격매2(JAK2)-신호전도여전록격활인자3(STAT3)통로적영향.방법 장건강웅성성년Wistar대서(체질량240～280g)수궤분위가수술조、결혈재관주손상조、결혈후처리조급결혈후처리+N-(2-구기병선기)-감안산(MPG)조.TUNEL법검측심기세포조망비솔;면역조직화학법검측bcl-2급bcl-xL단백수평;Western blot법검측린산화STAT3수평.결과 여결혈재관주손상조비교,결혈후처리현저상조재관주후bcl-2(42.4±5.6비8.6±2.4,P＜0.05)급bcl-xL(19.9±3.2비9.6±2.5,P＜0.05)수평,억제재관주후심기세포조망(37.8±4.0비56.9±6.0,P＜0.05).결혈후처리+MPG조교결혈후처리조bcl-2(10.5±2.1비42.4±5.6,P＜0.05)급bcl-xL(9.9±2.3비19.9±3.2,P＜0.05)수평현저강저,심기세포조망비솔현저승고(55.7±7.7비37.8±4.0,P＜0.05).결혈후처리현저상조재관주후린산화STAT3수평(0.27±0.02비0.43±0.08,P＜0.05).결혈후처리전사용MPG현저강저STAT3린산화수평(0.27±0.04비0.43±0.08,P＜0.05),억제JAK2-STAT3통로활성.결론 ROS재결혈후처리항심기세포조망작용중구유중요작용.결혈후처리가능통과양화환원신호격활JAK2-STAT3통로,병진일보조절STAT3하유bcl가족항조망단백표체수평이발휘항조망작용.
Objective To evaluate the role of reactive oxygen species (ROS) in the anti-apoptotic effect of postconditioning, and to investigate the effects of ROS on janus kinase 2 (JAK2) -signal transducer and activators of transcription 3 ( STAT3 ) pathway in postconditioning. Methods Healthy adult male Wistar rats were divided into four groups: sham group, ischemia/reperfusion injury (I/R) group, postconditioning group, and postconditioning + N- (2-mercaptopropionyl) -glycine (MPG) group. Myocardial apoptosis index was analyzed by TUNEL staining, and bcl-2 and bcl-xL levels were detected by immunohistochemistry after reperfusion. Western blotting was used to detect the phosphorylated STAT3. Results Postcondtioning significantly reduced myocardial apoptosis (37. 8 ± 4. 0 vs 56. 9 ± 6. 0, P ＜ 0. 05 ) after reperfusion, increased bcl-2 (42.4 ±5.6 vs 8.6 ±2.4,P＜0.05) and bcl-xL (19.9 ±3.2 vs 9.6 ±2.5,P＜0. 05 ) levels, and activated JAK2-STAT3 pathway (0. 27 ± 0. 02 vs 0. 43 ± 0. 08, P ＜ 0. 05 ) as compared with I/R group. Administration of MPG significantly attenuated the anti-apoptotic effect of postconditioning (55.7 ± 7.7 vs 37. 8 ± 4. 0, P ＜ 0. 05 ), decreased bcl-2 ( 10. 5 ± 2. 1 vs 42.4 ± 5.6, P ＜ 0. 05 ) and bclxL (9. 9 ±2. 3 vs 19. 9 ±3.2,P ＜0. 05 ) levels as compared with postconditioning group. MPG also decreased p-STAT3 levels (0. 27 ± 0. 04 vs 0. 43 ± 0. 08, P ＜ 0. 05 ) after reperfusion as compared with postconditioning group. Conclusion ROS plays essential roles in cardioprotection of postconditioning. Postconditioning may activate JAK2-STAT3 pathway and suppress apoptosis after reperfusion via a redox signaling.