摘要
目的:探究川芎嗪对心肌缺血再灌注的保护作用与机制。方法:结扎SD大鼠左冠状动脉前降支,缺血30 min后再灌注60 min建立心肌缺血再灌注模型,将造模成功的大鼠随机分为4组,分别为对照组(IR组)、川芎嗪治疗组(Lig组)、川芎嗪治疗且Janus酪氨酸蛋白激酶2(JAK2)抑制剂AG490处理组(Lig-AG组)及AG490处理组(AG组)。通过传感器检测左心室舒张压(LVDP)、心率(HR)、左心室压力微分(±dp/dt_(max))及冠脉血流量(CF);TTC染色法检测心肌梗死面积;TUNEL染色法检测心肌细胞凋亡;线粒体膜电位检测试剂盒检测线粒体膜电位变化;丙二醛(MDA)测定试剂盒、总超氧化物歧化酶(SOD)测定试剂盒、过氧化氢(H_(2)O_(2))测定试剂盒及总谷胱甘肽(T-GSH)/氧化型谷胱甘肽(GSSG)测定试剂盒分别检测MDA、SOD、H_(2)O_(2)的表达及GSH/GSSG比值;Western blot检测JAK2、STAT3、Bcl2及Bax蛋白表达。结果:与IR组相比,Lig组LVDP、HR、±dp/dt_(max)和CF明显升高,心肌组织氧化应激指标SOD活性、Eh水平及线粒体膜电位明显增加,JAK2、STAT3、Bcl2蛋白表达明显升高,心肌梗死面积、心肌细胞凋亡率明显减少,心肌组织中MDA、H_(2)O_(2)水平及Bax蛋白表达明显降低,差异具有统计学意义(P<0.05);与Lig组相比,Lig-AG组、AG组LVDP、HR、±dp/dt_(max)和CF水平明显降低,心肌组织氧化应激指标SOD活性、Eh水平及线粒体膜电位明显降低,JAK2、STAT3、Bcl2蛋白表达明显下降,心肌梗死面积、心肌细胞凋亡率明显升高,心肌组织中MDA、H_(2)O_(2)水平及Bax蛋白表达明显升高,差异具有统计学意义(P<0.05)。结论:川芎嗪可缓解心肌缺血再灌注损伤,其机制可能与对线粒体自噬及JAK2/STAT3信号通路的调控有关。
Objective:To investigate the protective effect and mechanism of ligustrazine on myocardial ischemia-reperfusion injury.Methods:SD rats were ligated with the anterior descending branch of the left coronary artery and reperfusion for 60 min after 30 min of ischemia to establish a scheme-induced ischemia reperfusion model.Rats with successful modeling were randomly divided into 4 groups,namely control group(IR group),ligustrazine treatment group(Lig group),ligustrazine treatment and treatment with Janus tyrosine kinase 2(JAK2)inhibitor AG490 group(Lig-AG group)and AG490 treatment group(AG group).Left ventricular diastolic pressure(LVDP),heart rate(HR),left ventricular pressure differential(+dp/dt_(max))and coronary flow(CF)were measured by sensors.The area of myocardial infarction was measured by TTC staining.Myocardial apoptosis was detected by TUNEL staining.Changes of mitochondrial membrane potential were detected by mitochondrial membrane potential detection kit.Malondialdehyde(MDA)assay kit,total superoxide dismutase(SOD)assay kit,hydrogen peroxide(H_(2)O_(2))assay kit and total glutathione(T-GSH)/oxidized glutathione(GSSG)assay kit were used to detect expressions of MDA,SOD,H_(2)O_(2)and GSH/GSSG ratio,respectively.Western blot was used to detect expression of JAK2,STAT3,Bcl2 and Bax protein.Results:Compared with IR group,LVDP Lig group,HR,±dp/dt_(max)and CF increased significantly,SOD activity of myocardial tissue oxidative stress index,level of Eh,and obviously increase the mitochondrial membrane potential and JAK2 and STAT3 and Bcl2 protein expression significantly increases,myocardial infarction area,significantly reduce the myocardial cell apoptosis rate,MDA,H_(2)O_(2) levels in the myocardial tissue and Bax protein expression significantly reduced,statistically significant difference(P<0.05).Compared with Lig group,LVDP Lig-AG group,AG group,HR,±dp/dt_(max)and CF decreased obviously,and myocardial tissue SOD activity of oxidative stress indicators,significantly lower level of Eh and mitochondrial membrane potential,JAK2 and STAT3 and Bcl2 protein expression decreased obviously,and myocardial infarction area,myocardial apoptosis rate increased significantly,the myocardial tissue of MDA,H_(2)O_(2) levels and Bax protein expression significantly increases,statistically significant difference(P<0.05).Conclusion:Ligustrazine can alleviate myocardial ischemia-reperfusion injury,which may be related to the regulation of mitochondrial autophagy and JAK2/STAT3 signaling pathway.
作者
陈乘波
陈天宝
许友榜
CHEN Cheng-Bo;CHEN Tian-Bao;XU You-Bang(Department of Cardiology,Quanzhou First Hospital Affiliated to Fujian Medical University,Quanzhou 362000,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2021年第7期819-823,共5页
Chinese Journal of Immunology
