番茄红素激活JAK/STAT3信号通路减轻离体大鼠心脏缺血再灌注损伤  

Lycopene alleviates myocardial ischemia reperfusion injury in isolated rat hearts via activating JAK/STAT signaling pathway

作　　者：李旭影 吴楠[2] 刘爽[1] 黄梓俊 苗嘉芯 贾大林[1] LI Xu-ying;WU Nan;LIU Shuang;HUANG Zi-jun;MIAO Jia-xin;JIA Da-lin(Department of Cardiovascular,the 1 st Affiliated Hospital of China Medical University,Shenyang 110001,China)

机构地区：[1]中国医科大学附属第一医院心血管内科,辽宁沈阳110001 [2]中国医科大学附属第一医院中心实验室,辽宁沈阳110001

出　　处：《解剖科学进展》2018年第5期513-517,共5页Progress of Anatomical Sciences

基　　金：国家自然科学基金(81670320);辽宁省自然科学基金(201602826)

摘　　要：目的探讨番茄红素对离体大鼠心脏缺血再灌注损伤的心肌保护作用及其可能的机制。方法 SPF级Wistar大鼠65只,随机分为缺血再灌注组(IR组)、药用玉米油组(Vehicle组)、40mg/kg番茄红素组(LP40组)。采用Langendorff灌流装置缺血30min、再灌注60min建立离体大鼠心脏缺血再灌注模型;IR组缺血30min,复灌60min;Vehicle组按每只大鼠2ml药用玉米油予大鼠皮下连续注射5d; LP40组番茄红素按40mg/kg,溶于2ml药用玉米油后皮下注射入大鼠体内,连续注射5d。于术中记录冠脉流量、心率;TTC染色测定心肌梗死面积;TUNEL染色检测心肌细胞凋亡;Western blot检测线粒体相关凋亡蛋白、磷酸化的JAK和STAT蛋白表达;线粒体膜通道孔光度法检测量化MPTP开放程度。结果与IR组相比,LP40组冠脉流量及心率于再灌注后显著恢复;心梗面积百分比、心肌细胞凋亡比例均降低;线粒体相关凋亡蛋白:cytochrome C、APAF-1、cleaved caspase-9、cleaved caspase-3表达水平均下降;心肌线粒体对钙离子诱导MPTP开放的敏感性下降(P<0.05),磷酸化的JAK和STAT表达水平增加(P<0.05)。结论番茄红素预处理减轻离体大鼠心脏缺血再灌注损伤可能与激活JAK/STAT信号通路相关。Objective To explore the protective effect and possible mechanism of lycopene on the myocardial ischemia reperfusion injury in isolated Wistar rat heart. Methods 65 SPF Wistar rats were randomly divided into ischemia-reperfusion group（IR group）, medicinal corn oil group（Vehicle group） and 40 mg/kg lycopene group（LP40 group）. The model isolated rat heart ischemia-reperfusion was established by Langendorff perfusion device, ischemia for 30 min and reperfused for 60 min, lycopene was injected subcutaneously into rats in 40 mg/kg with dissolved in 2 ml medicinal corn oil for 5 days. The coronary flow rate and heart rate were recorded during the operation, myocardial infarction area was measured by TTC staining, and apoptosis of myocardial cells was detected by TUNEL staining. Western blot was used to detect theexpression of the mitochondrial related apoptotic proteins and the phosphorylation of JAK and STAT proteins. Mitochondrial membrane pore channel photometric detection kit was used to quantify MPTP opening. Results Compared with IR group, the coronary flow and heart rate recovered, the percentage of myocardial infarction area and myocardial cell apoptosis decreased, the expression levels of mytochrome C, APAF-1, cleaved caspase-9 and cleaved caspase-3 proteins decreased, and the sensitivity of myocardial mitochondria to the opening of calcium induced MPTP decreased, but the expression levelof phosphorylated JAK and STAT proteins increased（P 〈0.05） in LP40 group. Conclusion Lycopene preconditioningalleviated the ischemia-reperfusion injury of isolated rat hearts, which might be related to activating JAK/STAT signalingpathway.

关 键 词：番茄红素 心肌缺血再灌注损伤 JAK/STAT WISTAR大鼠 

分 类 号：R541.4[医药卫生—心血管疾病]