Metallothionein mediates cardioprotection of isoliquiritigenin against ischemia-reperfusion through JAK2/STAT3 activation  

作　　者：Wei AN Jing YANG Ying AO 

机构地区：[1]Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071, China

出　　处：《Acta Pharmacologica Sinica》2006年第11期1431-1437,共7页中国药理学报（英文版）

摘　　要：Aim： To examine whether isoliquiritigenin （ISL） can attenuate myocardial ischemiareperfusion （MI/R） injury in rats by inducing metallothionein （MT） through activation of janus kinase 2 （JAK 2）/signal transducers and activators of transcription 3 （STAT 3） pathway. Methods： The experimental model of MI/R in rats was generated by 30 min of ischemia and reperfusion for 2 h. The mRNA expression of MT, COX-2, and iNOS were measured by RT-PCR. The protein expressions of MT, JAK/STAT, extracellular signal-regulated kinase （ERK）, and Akt were determined by Western blotting in the absence or presence of a JAK kinase inhibitor, tyrphostin AG490 （1.0 mg/kg, iv, 1 h before ischemia）. Results： Pretreatment with ISL markedly decreased the severity of reperfusion-induced arrhythmias and myocardial infarct size. In the ISL 20 mg/kg group, the activities of lactate dehydrogenase （LDH） and creatinine phosphokinase （CPK） were reduced by 38.4% and 51.3% when compared with the vehicle group. Increased JAK 2/STAT 3 phosphorylation was accompanied by increased synthesis of MT but not of COX-2 or iNOS in ISL-treated groups. AG490 can significantly weaken ISL-induced cardioprotection and prevent the increase of MT expression and JAK 2/STAT 3 phosphorylation. Conclusion： ISL protected MI/R injury through activation of JAK 2/STAT 3 signal transduction pathway, which might be involved in mediating the upregulation of MT expression.Aim： To examine whether isoliquiritigenin （ISL） can attenuate myocardial ischemiareperfusion （MI/R） injury in rats by inducing metallothionein （MT） through activation of janus kinase 2 （JAK 2）/signal transducers and activators of transcription 3 （STAT 3） pathway. Methods： The experimental model of MI/R in rats was generated by 30 min of ischemia and reperfusion for 2 h. The mRNA expression of MT, COX-2, and iNOS were measured by RT-PCR. The protein expressions of MT, JAK/STAT, extracellular signal-regulated kinase （ERK）, and Akt were determined by Western blotting in the absence or presence of a JAK kinase inhibitor, tyrphostin AG490 （1.0 mg/kg, iv, 1 h before ischemia）. Results： Pretreatment with ISL markedly decreased the severity of reperfusion-induced arrhythmias and myocardial infarct size. In the ISL 20 mg/kg group, the activities of lactate dehydrogenase （LDH） and creatinine phosphokinase （CPK） were reduced by 38.4% and 51.3% when compared with the vehicle group. Increased JAK 2/STAT 3 phosphorylation was accompanied by increased synthesis of MT but not of COX-2 or iNOS in ISL-treated groups. AG490 can significantly weaken ISL-induced cardioprotection and prevent the increase of MT expression and JAK 2/STAT 3 phosphorylation. Conclusion： ISL protected MI/R injury through activation of JAK 2/STAT 3 signal transduction pathway, which might be involved in mediating the upregulation of MT expression.

关 键 词：ISOLIQUIRITIGENIN myocardial ischemiareperfusion METALLOTHIONEIN janus kinase STAT3 transcription factors 

分 类 号：R96[医药卫生—药理学]