张力俨,耿国英,宋付凯,蒋友旭,杨东慧,马延仃

• 1:河南中医药大学第五临床医学院
• 2:郑州人民医院
• 3:郑州大学第二附属医院

摘要(Abstract)：

目的:探讨片仔癀改善心力衰竭(heart failure,HF)的作用机制。方法:采用H9c2心肌细胞建立氧糖剥夺(oxygen and glucose deprivation,OGD)诱导的心肌细胞损伤模型;采用左前降支冠状动脉结扎法建立心力衰竭小鼠模型，并给予相应药物干预。采用M型超声心动图和动物超声系统测量小鼠舒张末期左室后壁厚度(left ventricular posterior wall thickness at enddiastole,LVPWd)、左室舒张末内径(left ventricular end-diastolic diameter,LVEDD)、左室收缩末内径(left ventricular end-systolic diameter,LVESD)和舒张末期左室前壁厚度(left ventricular anterior wall thickness at end-diastole,LVAWd)，并计算左室短轴缩短率(left ventricular fractional shortening,LVFS)和左室射血分数(left ventricular ejection fraction,LVEF);采用马松染色和HE染色分析小鼠心脏组织病理损伤; CCK-8法检测细胞增殖;流式细胞术检测细胞凋亡; ELISA法检测小鼠血清和细胞培养上清液中TNF-α、IL-6和IL-1β的表达水平; Western Blot检测细胞与心肌组织中B淋巴细胞瘤-2(B-cell lymphoma/leukemia-2,Bcl-2)、Bcl-2相关X蛋白(Bcl-2-associated X protein,BAX)、半胱天冬氨酸蛋白酶3(Caspase-3)、腺苷酸活化蛋白激酶(adenosine monophosphate-activated protein kinase,AMPK)、UNC-51样激酶1(UNC-51-like kinase 1,ULK1)的蛋白表达水平; LD-P比色法检测乳酸脱氢酶(lactate dehydrogenase,LDH)的水平。结果:动物实验发现:与模型组比较，片仔癀显著改善了小鼠心肌组织病理变化，降低心肌梗死面积;显著升高LVEF、LVFS、LVAWd和LVPWd水平，显著降低LVEDD及LVESD水平;显著降低血清中TNF-α、IL-6和IL-1β的水平;显著升高心肌组织中Bcl-2的表达水平，显著降低Bax及cleaved-Caspase-3的表达水平;细胞实验发现:与模型组比较，片仔癀组可显著促进细胞增殖并抑制细胞凋亡;显著降低细胞培养上清液中TNF-α、IL-6和IL-1β的水平;显著抑制LDH的释放;显著升高Bcl-2的表达水平，显著降低Bax及cleaved-Caspase-3的表达水平。此外，片仔癀还可显著升高心肌组织和细胞中AMPK和ULK1的磷酸化水平; AMPK信号通路抑制后，片仔癀对细胞增殖、凋亡、LDH的抑制作用和抗炎作用均显著减弱，差异均具有统计学意义(P<0.05)。结论:片仔癀通过激活AMPK-ULK1信号通路，改善心功能、抑制炎症反应与心肌细胞凋亡，缓解心力衰竭。

关键词(KeyWords)： 心力衰竭;片仔癀;AMPK-ULK1信号通路;细胞增殖;细胞凋亡;大鼠

Abstract:

Keywords:

基金项目(Foundation): 2024年度河南省医学科技攻关计划联合共建项目(LHGJ20240886)

作者(Author): 张力俨,耿国英,宋付凯,蒋友旭,杨东慧,马延仃

DOI: 10.16367/j.issn.1003-5028.2025.12.0297

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