sarcK_(ATP)和K_(Ca)参与由高铁血红素诱导的心肌缺血复灌性损伤的保护作用

Involvement of sarcKATP and Kca in hemin induced cardioprotection in rat hearts

目的:探讨sarcKATP和KCa参与高铁血红素(heme)诱导血红素氧化酶1(HO-1)活性增加对心肌缺血复灌性损伤的保护作用。方法:离体大鼠心脏行Langendorff灌流,给予30min缺血和2h复灌,观察心室收缩功能、LDH、CK和心肌梗死等指标。结果:腹腔注射HO-1的诱导剂高铁血红素24h后,可明显改善缺血/复灌心脏的收缩功能,减少复灌期LDH和CK释放,缩小心肌梗死面积。在腹腔注射高铁血红素前给予胞膜KATP通道(sarcKATP通道)的阻断剂HMR-1098可取消高铁血红素引发的心肌保护作用。在高铁血红素预处理后24h,缺血/复灌前10min给予钙激动的钾通道(Kca通道)的阻断剂Paxiline与高铁血红素组相比,心肌梗死面积扩大,心脏收缩功能下降。结论:高铁血红素可诱导HO-1活性增加并对抗心肌缺血复灌性损伤,sarcKATP通道和KCa通道在其中同时作为启动因子参与高铁血红素诱导的晚期心肌保护作用。

Objective： To investigate sarc KATP and KCa are involved in the cardioprotective effects. Methods： Infarct size was measured in isolated rat hearts following occlusion of the left anterior descending coronary artery for 30 min and subsequent reperfusion for 2 h. The ventricular function, LDH and CK during ischemia/reperfusion period were also observed. Results： Infarct size, LDH and CK were reduced in the heroin （50 micrograms/kg） group compared with the control group. The myocardial performance was also improved in hemin group. Whereas HMR-1098 （a blocker of sarcolemmal ATP-sensitive potassium channel （sarcKATP）） administered before heroin preconditioning abolished the protective effect, the blocker of calcium activated potassium channel （KCa channel） for 10 min before I/R led to larger infarct sizes and poorer myocardial performance as compared with the hemin group. Conclusion： sarcKATP channels are required as a trigger for delayed cardioprotection induced by heroin. The opening of KCa channels-dependent mechanism also participates in the protection.