利多卡因对大鼠缺血-再灌注心律失常的影响及机制探讨  

Effects and mechanism of lidocaine on ischemia-reperfusion arrhythmia in rats

作　　者：王静[1] 唐玲[1] 肖婷[1] WANG Jing;TANG Ling;XIAC Ting(Department of Anesthesiology and Surgery,Hunan Children's Hospital,Changsha 410007,Hunan,China)

机构地区：[1]湖南省儿童医院麻醉手术科,湖南长沙410007

出　　处：《中国心脏起搏与心电生理杂志》2023年第2期135-141,共7页Chinese Journal of Cardiac Pacing and Electrophysiology

基　　金：2021年度湖南省卫生健康委科研立项课题(202104111245)。

摘　　要：目的利多卡因对大鼠缺血-再灌注心律失常的影响及机制。方法制备大鼠缺血-再灌注心律失常模型,将其随机分为模型组、利多卡因低剂量(4 mg/kg)组、利多卡因高剂量(8 mg/kg)组、利多卡因(8 mg/kg)+磷脂酰肌醇3-激酶(PI3K)抑制剂LY294002(10 mg/kg)组,每组12只大鼠,另取12只大鼠设为假手术组,所有大鼠经药物分组干预处理后,比较各组心室颤动(简称室颤)持续时间、室性早搏(简称室早)次数;采用TUNEL染色检测各组大鼠心肌细胞凋亡率;采用试剂盒检测各组大鼠心肌组织氧化应激因子谷胱甘肽过氧化物酶(GSH-Px)、活性氧(ROS)、丙二醛(MDA)及血清促炎因子诱导型一氧化氮合酶(iNOS)、前列腺素E2(PGE2)水平;采用免疫印迹实验检测各组大鼠心肌组织凋亡蛋白、自噬蛋白、PI3K/AKT通路相关蛋白表达。结果与假手术组相比,模型组大鼠室颤持续时间、室早次数、心肌细胞凋亡率、心肌组织ROS及MDA、血清iNOS及PGE2水平、心肌组织凋亡蛋白(Bax、caspase-9)与自噬蛋白(LC3Ⅱ/LC3Ⅰ与Beclin-1)表达水平显著升高(P<0.05),心肌组织GSH-Px水平、PI3K/AKT通路蛋白p-PI3K/PI3K及p-AKT/AKT水平显著降低(P<0.05);与模型组相比,利多卡因低剂量与高剂量组大鼠室颤持续时间、室早次数、心肌细胞凋亡率、心肌组织ROS及MDA、血清iNOS及PGE2水平、心肌组织凋亡蛋白(Bax、caspase-9)与自噬蛋白(LC3Ⅱ/LC3Ⅰ与Beclin-1)表达水平均降低(P<0.05),心肌组织GSH-Px水平、PI3K/AKT通路蛋白p-PI3K/PI3K及p-AKT/AKT水平均升高(P<0.05);与利多卡因低剂量组相比,利多卡因高剂量组大鼠室颤持续时间、室早次数、心肌细胞凋亡率、心肌组织ROS及MDA、血清iNOS及PGE2水平、心肌组织凋亡蛋白(Bax、caspase-9)与自噬蛋白(LC3Ⅱ/LC3Ⅰ与Beclin-1)表达水平降低(P<0.05),心肌组织GSH-Px水平、PI3K/AKT通路蛋白p-PI3K/PI3K及p-AKT/AKT水平升高(P<0.05);与利多卡因高剂量组相比,利多卡�Objective To investigate the effects and mechanism of lidocaine on ischemia-reperfusion arrhythmia in rats.Methods A rat ischemia-reperfusion arrhythmia model was prepared and randomly divided into model group,low-dose lidocaine(4 mg/kg)group,the high-dose lidocaine(8 mg/kg)group and lidocaine(8 mg/kg)+phosphatidylino sitol3-kinase(PI3K)inhibition(10 mg/kg)group,with 12 rats in each group,and another 12 rats were set as sham operation group.After all rats were treated with drug intervention,the rats'arrhythmia symptoms were evaluated,and the duration of ventricular fibrillation and the number of ventricular premature beats in each group were compared;TUNEL staining was used to detect the apoptosis rate of rat cardiomyocytes in each group;kit was used to detect the levels of oxidative stress factors glutathione peroxidase(GSH-Px),reactive oxygen species(ROS),malondialdehyde(MDA)and serum pro-inflammatory factors inducible nitric oxide synthase(iNOS)and prostaglandin E2(PGE2)in myocardial tissue of rats in each group;Western blotting was used to detect the expression of apoptotic protein,autophagy protein PI3 K/AKT pathway related proteins in myocardial tissues of rats in eachgroup.Results Compared with the sham operation group,the duration of ventricular fibrillation,the number of premature ventricular beats,myocardial cell apoptosis,myocardial tissue ROS and MDA,serum iNOS and PGEz levels,and the expression levels of apoptotic proteins(Bax,caspase-9)and autophagic proteins(LC3II/LC3I and Beclin-1)were significantly increased in the model group(P<0.05),the myocardial tissue GSHPx level,PI3K/AKT pathway protein p-PI3K/PI3K and p-AKT/AKT levels were significantly reduced(P<0.05);Compared with the model group,the duration of ventricular fibrillation,the number of premature ventricular beats,myocardial cell apoptosis,myocardial tissue ROS and MDA,serum iNOS and PGEz levels,and the expression levels of apoptotic proteins(Bax,caspase-9)and autophagic proteins(LC3II/LC3I and Beclin-1)were reduced in the Lidocaine adminis

关 键 词：心血管病学 利多卡因 缺血-再灌注 心律失常 磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT) 

分 类 号：R541.7[医药卫生—心血管疾病] R972.2[医药卫生—内科学]