摘要
目的探讨非肽类孤啡肽受体(ORL1)拮抗剂compound-24(C-24)对大鼠急性心肌缺血后心律失常的影响。方法50只清洁级健康雄性SD大鼠按照随机数字表法分为假手术组(Sham组)、冠脉结扎组(CAO组)和C-24组(C组),C组内设3个亚组,即C-Ⅰ组(1×10^-13 mol/L)、C-Ⅱ组(1×10^-11 mol/L)、C-Ⅲ组(1×10^-9 mol/L)。CAO组和C组结扎冠状动脉左前降支制备大鼠急性心肌缺血模型,C组各亚组于结扎前10 min经尾静脉注射相应浓度C-24。记录各组大鼠结扎后15 min内的心率变异性(HRV)及心功能指标并进行心律失常评分。冠脉结扎15 min后处死动物并取心肌组织,酶联免疫吸附测定(ELISA)法检测大鼠心肌肿瘤坏死因子(TNF)-α及白细胞介素(IL)-1β水平并分析室性早搏(VEB)发生次数和TNF-α、IL-1β的相关性。结果与Sham组比较,CAO组冠脉闭塞后15 min内VEB次数明显增加,室速(VT)+室颤(VF)发生次数增加,持续时间延长,心律失常评分升高(P<0.05);同时HRV指标中RR间期标准差(SDNN)、相临RR间期差的均方根(RMSSD)均明显降低(P<0.05),低高频比值(LF/HE)升高(P<0.05),心肌组织TNF-α和IL-1β水平明显升高。而与CAO组比较,C-Ⅰ组、C-Ⅱ组、C-Ⅲ组VEB发生次数明显减少,C-Ⅲ组VT+VF发生次数减少,持续时间缩短,心律失常评分和LF/HF下降(P<0.05)。此外C-Ⅱ组和C-Ⅲ组心肌组织TNF-α和IL-1β水平较CAO组明显下降。相关性分析显示,TNF-α和IL-1β水平与VEB发生次数均呈线性正相关关系(r分别为0.620、0.609,P<0.01)。实验期间5组大鼠左心室收缩压(LVSP)、左心室舒张末压(LVEDP)、心率(HR)、左心室压力上升和下降最大变化率(±dp/dtmax)差异均无统计学意义。结论C-24可减少急性心肌缺血后心律失常的发生以及心肌组织中炎性因子的产生,且对心功能无明显影响。
Objective To explore the effect of compound-24(C-24),a non-peptide orphanin receptor(ORL1)antagonist,on arrhythmia after acute myocardial ischemia in rats.Methods A total of 50 clean-grade healthy male SD rats were divided into 5 groups according to the random number table method,including sham operation group(Sham group),coronary artery ligation group(CAO group)and C-24 group(C group).The C group was divided into three subgroups,namely C-I group(1×10^-13 mol/L),C-Ⅱ group(1×10^-11 mol/L)and C-Ⅲ group(1×10^-9 mol/L).The left anterior descending coronary artery was ligated to prepare the rat model of acute myocardial ischemia in the CAO group and C-24 group.The three subgroups of C-24 were injected with the corresponding concentrations of C-24 via the tail vein at 10 min before ligation.The heart rate variability(HRV)indicators,cardiac function data and score arrhythmia within 15 minutes after ligation were recorded in each group of rats.After 15 minutes of coronary artery ligation,the rats were sacrificed and myocardial tissues were collected.Enzyme-linked immunosorbent assay(ELISA)was used to detect the concentrations of the rat myocardial inflammatory factors,tumor necrosis factor-α (TNF-α)and interleukin 1β(IL-1β).The correlation between the number of ventricular premature beats and TNF-α and IL-1β was analyzed.Results Compared with the Sham group,the number of VEBs increased significantly within 15 minutes after coronary artery occlusion,the number of occurrence of ventricular tachycardia(VT)+ventricular fibrillation(VF)increased and the duration was prolonged,and the arrhythmia score increased in the CAO group(P<0.05).The standard deviation of the RR interval(SDNN)and the root mean square(RMSSD)of the adjacent RR interval difference in HRV indicators were significantly reduced(P<0.05).The ratios of low and high frequency(LF/HE)increased(P<0.05),and the levels of TNF-α and IL-1β in myocardial tissue were significantly increased.Compared with the CAO group,the numbers of VEB occurrences were sign
作者
陈司坤
解梦莉
韩毅
郭政
CHEN Si-kun;XIE Meng-li;HAN Yi;GUO Zheng(School of Anesthesiology,Shanxi Medical University,Taiyuan 030000,China;Department of Anesthesiology,the Second Hospital of Shanxi Medical University)
出处
《天津医药》
CAS
北大核心
2021年第1期11-15,共5页
Tianjin Medical Journal
基金
国家自然科学基金资助项目(81400260)
山西省应用基础研究基金项目(201701D12111145)。
