熊果酸预处理对急性心肌缺血再灌注损伤的保护作用  

Protective Effect of Ursolic Acid Pretreatment on Acute Myocardial Ischemia-Reperfusion Injury

作　　者：谢剑琳[1] 吕君楠 胡洁 杨晓龙[1] XIE Jianlin;LYU Junnan;HU Jie;YANG Xiaolong(Handan Central Hospital,Handan Hebei China 056000)

机构地区：[1]邯郸市中心医院,河北邯郸056000

出　　处：《中医学报》2021年第2期371-376,共6页Acta Chinese Medicine

基　　金：邯郸市科学技术研究与发展计划项目(1823208043ZC)。

摘　　要：目的:研究熊果酸预处理对大鼠急性心肌缺血再灌注(I/R)损伤的保护作用并探讨其机制。方法:120只SD大鼠随机分为假手术组,I/R组,熊果酸低、中、高剂量(20 mg·kg^-1、40 mg·kg^-1、80 mg·kg^-1)组和维拉帕米(2.5 mg·kg^-1)组,采用结扎冠状动脉左前降支的方法复制急性心肌I/R大鼠模型。假手术组行手术通路但不结扎,术前7 d开始预给药处理。再灌注24 h后监测心电图ST段变化,超声影像系统测定心功能指标,HE染色法观察心肌组织病理学变化并行损伤评分,测定心脏梗死体积,心肌组织抗氧化酶活性和丙二醛(monochrome display adapter,MDA)的含量,心肌组织炎症因子水平。结果:熊果酸中、高剂量和维拉帕米组可抑制急性心肌I/R大鼠心电图ST段抬高,抑制舒张/收缩末期左室内径(LVIDd、LVIDs)升高和短轴缩短率(fraction shortening,FS)、射血分数(ejection fraction,EF)、每搏输出量(stroke volume,SV)降低,抑制心肌组织细胞病理性形态结构改变和损伤评分的升高,抑制心脏梗死体积百分比升高,抑制抗氧化酶[超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)]活性的降低和MDA含量的升高,抑制炎症因子[肿瘤坏死因子-α(tumor necrosis factor,TNF-α)、细胞间黏附分子-1(intercellular cell adhesion molecule-1,ICAM-1),白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)]水平的升高;较I/R组差异均具有统计学意义(P<0.05;P<0.01)。结论:熊果酸预处理对急性心肌I/R损伤大鼠心功能和心肌组织损伤具有保护作用,其机制可能与抑制氧化应激损伤和炎症级联反应有关。Objective:To explore the protective effect and mechanism of ursolic acid pretreatment on acute myocardial ischemia-reperfusion(I/R)injury in rats.Methods:120 SD rats were randomly divided into sham operation group,I/R group,ursolic acid low,medium and high(20 mg·kg^-1,40 mg·kg^-1,80 mg·kg^-1)dose group,and Verapamil(2.5 mg·kg^-1)group.The rat model of acute myocardial I/R induced by ligating the left anterior descending coronary artery in rats.In the sham operation group,surgical was performed without ligation,and pre-dose treatment was started 7 days before the operation.After 24 hours of reperfusion,the ST-segment changes of ECG were monitored and the cardiac function indexes were measured by the ultrasound imaging system.HE staining was used to observe the pathological changes and rate the damage level of the myocardium,determine the volume of myocardial infarction,myocardial antioxidant enzyme activity,the level of monochrome display adapter(MDA),and the level of myocardial inflammatory factors.Results:The medium and high doses of ursolic acid and the verapamil group can inhibit the ST-segment elevation of acute myocardial I/R in rats,restrain the elevation of LVIDd、LVIDs,and curb the decrease of fraction shortening(FS),ejection fraction(EF),stroke volume(SV).They also reduce the pathological morphological structure changes of the myocardium and lower the injury rates,decrease the percentage of cardiac infarction volume,inhibit the activity decrease of antioxidant enzymes[superoxide dismutase(SOD),catalase(CAT)],lower MDA,and reduce the level of inflammatory factors[tumor necrosis factor(TNF-α),intercellular cell adhesion molecule-1(ICAM-1),interleukin-1β(IL-1β),interleukin-6(IL-6)].The differences were statistically significant(P<0.05;P<0.01)compared with the I/R group.Conclusion:Ursolic acid pretreatment can increase cardiac function and attenuate myocardium damage in rats with acute myocardial I/R injury,the mechanism of which may be associated with the inhibition of oxidative stress damage and in

关 键 词：熊果酸 急性心肌缺血 心功能 氧化应激 炎症反应 

分 类 号：R285.5[医药卫生—中药学]