摘要
目的探讨小檗碱(BBR)减轻大鼠心肌缺血再灌注(MI/R)损伤的作用及其与JAK2/STAT3信号通路的关系。方法雄性SD大鼠(250只)随机分为7组(n=36):假手术组(sham)、sham+BBR组、sham+AG490(AG,JAK2/STAT3通路抑制剂)组、MI/R+溶剂组(MI/R+V)、MI/R+BBR组、MI/R+BBR+AG组、MI/R+AG组。常规结扎大鼠冠状动脉左前降支行心肌缺血再灌注手术,缺血30 min后再灌注4 h,用Western blot法检测心肌JAK2、STAT3磷酸化水平及心肌凋亡相关蛋白表达,再灌注6 h后检测心肌细胞凋亡率、梗死面积及氧化应激相关指标,再灌注72 h后检测心功能。结果 BBR可显著改善心肌缺血再灌注术后心功能并减轻心肌凋亡及梗死,这种保护作用可被AG阻断(均P<0.05)。BBR治疗还可显著提高心肌JAK2及STAT3磷酸化水平,抑制凋亡相关信号分子表达,这种作用也被AG阻断(P<0.05)。结论 BBR可显著减轻大鼠MI/R损伤后心肌梗死及凋亡水平,改善心功能,JAK2/STAT3可能介导此作用。
Objective To determine the protective effect of berberine（ BBR） on myocardial ischemia / reperfusion（ MI/R） injury in rats and the role of JAK2 /STAT3 signaling pathway in this process. Methods Male SpragueDawley rats were randomly divided into 7 groups（ n = 36） ： sham,sham ＋ BBR,sham ＋ AG（ AG490,the inhibiter of JAK2 / STAT3 signaling pathway）,MI / R ＋ V（ vehicle）,MI / R ＋ BBR,sham ＋ BBR ＋ AG and MI / R ＋ AG,and then exposed to MI / R insult. After 4 h of reperfusion,myocardial p-JAK2 / JAK2 and p-STAT3 / STAT3 ratios,and the apoptotic related protein expression were assessed. 6 h after reperfusion,myocardial apoptotic index and infarct size were evaluated. The cardiac function were measured 72 h after reperfusion. Results BBR treatmentsignificantly improved cardiac functional and reduced cardiomyocytes apoptosis. In addition,BBR treatment also activated JAK2 / STAT3 signaling and suppressed apoptotic signaling. However,these protective effects were all inhibited by AG treatment. Conclusions BBR attenuates MI / R injury by reducing apoptosis possibly via activating JAK2 /STAT3 signaling pathway.
出处
《基础医学与临床》
CSCD
2016年第4期433-438,共6页
Basic and Clinical Medicine
基金
国家十二五科技支撑计划(2011BAI11B20)
国家自然科学基金(81470415
81270170
81200151
81470411)
陕西省社会发展攻关计划(2015SF104
2012K15-02-01)
陕西省国际科技合作与交流计划(2015KW-047)
西京医院学科助推计划(XJZT14203
XJGX12C11
XJGX13LC15)
