从Toll样受体4和钠钾ATP酶探究利拉鲁肽对缺血再灌注损伤心肌的保护作用  

Protective effects of liraglutide for myocardial ischemia-reperfusion injury from Toll-like receptor 4 and Na^+/K^+-ATPase

作　　者：万欢[1] 李玲 任汉强[1] 马铭[1] 崔晓颖[1] WAN Huan;LI Ling;REN Han-qiang;MA Ming;CUI Xiao-ying(Department of Endocrinology, Wuhan Sixth Hospital/Affiliated Hospital of Jianghan University, Wuhan HUBEI 430015, China;Department of General Medicine, Wuhan Red Cross Hospital/Wuhan Eleventh Hospital, Wuhan HUBEI 430015, China)

机构地区：[1]武汉市第六医院/江汉大学附属医院内分泌科,湖北武汉430015 [2]武汉市红十字会医院/武汉市第十一医院综合内科,湖北武汉430015

出　　处：《中国新药与临床杂志》2018年第6期358-362,共5页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的从Toll样受体4(TLR4)和钠钾ATP酶探究利拉鲁肽对缺血再灌注损伤心肌的保护作用。方法将150只SD大鼠分为假手术组,模型组,利拉鲁肽低、中、高剂量(35、70、140μg·kg-1·d-1,术前7 d皮下注射,持续7 d)组以及正常对照组,结扎左前降支30 min,再灌注120 min制缺血再灌注模型。采用伊文思蓝染色法测定受试大鼠心肌梗死面积,ELISA法检测白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、内皮细胞型纤溶酶原激活物抑制因子-1(PAI-1)和核转录因子-κBp65(NF-κBp65)含量;Western blot检测TLR4蛋白表达;连续反应光谱法测定钠钾ATP酶活性。结果利拉鲁肽三个剂量组大鼠的心肌梗死面积均低于模型组(P<0.05),炎症因子IL-6、TNF-α、PAI-1浓度,TLR4、NF-κB p65蛋白表达水平以及钠钾ATP酶活性较模型组均发生了不同程度的下降,且呈剂量依赖性(P<0.05)。结论利拉鲁肽可能通过阻断TLR4/NF-κB信号通路,稳定钠钾ATP酶活性,起到保护缺血再灌注损伤心肌的作用。AIM To explore protective effects of liraglutide on myocardial ischemia-reperfusion injury from Toll-like receptor（TLR4） and Na~＋/K~＋-ATPase. METHODS One hundred and fifty SD rats were divided into sham group, ischemia reperfusion model group, low dose of liraglutide group, medium dose of liraglutide group, high dose of liraglutide group and control group. The rats of the liraglutide groups were injected with liraglutide 35, 70, 140 μg·kg^-1·d^-1 for 7 d before operation. The rats were ligated left anterior descending coronary artery for 30 min, reperfusion for 120 min to induce myocardial ischemia-reperfusion model. The area of myocardial infarction were measured by Evans blue staining. The levels of interleukin-6（ IL-6）, tumor necrosis factor alpha（ TNF-α）, endothelial cell plasminogen activator inhibitor-1（ PAI-1） and nuclear transcription factor kappa B p65（ NF-κB p65） were detected by ELISA assay. TLR4 protein expression were detected by Western blot. The activity of Na^＋/K^＋-ATPase was determined by continuous reaction spectrometry.RESULTS Compared with the model group, the area of myocardial infarction was lower in the three dose of liraglutide groups（P 〈0.05）. The levels of IL-6, TNF-α, PAI-1, TLR4, NF-κBp65 and the activities of Na^＋/K^＋-ATPase were decreased in the liraglutide groups in a dose-dependent manner compared with the model group（ P 〈0.05）. CONCLUSION Liraglutide could protect myocardial ischemia-reperfusion injury by inhibiting TLR4/NF-κB signaling pathway and stabilizing the activity of Na^＋/K^＋-ATPase.

关 键 词：利拉鲁肽 TOLL样受体4 钠钾交换ATP酶 再灌注损伤 

分 类 号：R972[医药卫生—药品]