早期输注艾司洛尔通过降低血乳酸抑制心肌细胞焦亡改善脓毒症心肌病  

Early Esmolol infusion can improve septic cardiomyopathy by reducing blood lactate and inhibiting cardiomyocytes pyroptosis

作　　者：温良鹤[1] 权震 李云龙[1] 王洪亮[1] 叶明[1] WEN Liang-he;QUAN Zhen;LI Yun-long;WANG Hong-liang;YE Ming(Department of Critical Care Medicine,the Second Affiliated Hospital of Harbin Medical University,Heilongjiang Harbin,150085,China;The Second Clinical Medical College of Harbin Medical University,Heilongjiang Harbin,150085,China)

机构地区：[1]哈尔滨医科大学附属第二医院重症医学科,黑龙江哈尔滨150085 [2]哈尔滨医科大学第二临床医学院,黑龙江哈尔滨150085

出　　处：《内科急危重症杂志》2024年第6期501-507,共7页Journal of Critical Care In Internal Medicine

基　　金：中华国际医学交流基金会(z-2016-23-2101-38);黑龙江省高校基本科研业务费资助项目(2023-KYYWF-0192)。

摘　　要：目的:验证艾司洛尔(ES)对脓毒症心肌病(SCM)的疗效,并探索其潜在机制。方法:研究对象为收治的68例SCM患者,经充分复苏后,将心率≥100次/min者随机分为ES组(34例)与对照组(34例),分析基线情况及转归。另外,选用48只雄性C57BL/6小鼠随机分为假手术组(Sham)、脓毒症模型组(Sepsis)、艾司洛尔治疗组(Sepsis+ES),各16只。记录生存情况,超声检测左室射血分数(LVEF)、血乳酸、乳酸脱氢酶(LDH)、心肌损伤标志物及炎症因子水平,通过HE染色检测组织病理学变化,使用Western blot检测蛋白泛乳酸化及焦亡相关蛋白(GSDMD-N、cl.caspase 1、NLRP3)水平。结果:ES组患者在ICU住院时间缩短,血乳酸水平降低。ES改善SCM小鼠的生存率,LVEF提高,血乳酸、LDH、肌酸激酶同工酶(CK-MB)及炎症因子水平降低,减轻心肌组织的病理学改变,减少蛋白泛乳酸化及GSDMD-N、cl.caspase 1、NLRP3的表达。外源性乳酸可以逆转ES的保护作用。结论:ES通过降低血乳酸水平,抑制心肌细胞的焦亡,从而改善SCM预后。Objective:This study aims to evaluate the efficacy of Esmolol(ES)in septic cardiomyopathy(SCM)and explore its potential mechanisms.Methods:The study subjects were patients with SCM.After adequate resuscitation,the patients with heart rate≥100 beats/min were randomly divided into ES group(n=34)and control group(n=34).Baseline characteristics and outcomes were analyzed.Additionally,48 male C57BL/6 mice were randomly divided into Sham,sepsis,and Esmolol treatment(sepsis+ES)groups to assess survival,echocardiographically measure left ventricular ejection fraction(LVEF),and evaluate blood lactate,lactate dehydrogenase(LDH),myocardial injury markers,and inflammatory factor levels.HE staining was used for histopathological analysis,and Western blotting was conducted to assess protein lactylation and levels of pyroptosis-related proteins(GSDMD-N,cl-caspase 1,NLRP3).Results:Patients in the ES group experienced a reduction in ICU stay duration and blood lactate levels.ES improved survival in SCM mice,enhanced LVEF,and reduced levels of blood lactate,LDH,creatine kinase-MB isoenzyme(CK-MB),and inflammatory factors.It alleviated histopathological changes in myocardial tissue,diminished protein lactylation and expression of GSDMD-N,cl-caspase 1,and NLRP3.Exogenous lactate was found to reverse the protective effects of ES.Conclusion:ES improves SCM by lowering blood lactate levels and inhibiting myocardial cell pyroptosis,with potential involvement of protein lactylation changes.

关 键 词：脓毒症心肌病 艾司洛尔 乳酸 乳酸化修饰 细胞焦亡 

分 类 号：R542.2[医药卫生—心血管疾病]