摘要： 目的 探讨Tubastatin A（Tub A）对脂多糖（LPS）刺激RAW264.7巨噬细胞导致心肌细胞氧化应激损伤的作用。方法 将H9C2心肌细胞分为3组：Sham组（用无LPS刺激的巨噬细胞所获上清液培养心肌细胞）、MCM组（用LPS刺激的巨噬细胞所获上清液培养心肌细胞，建立体外脓毒症心肌损伤模型）、Tub A组（Tub A预处理后，再用含Tub A经LPS刺激的巨噬细胞所获上清液培养心肌细胞）。3组心肌细胞培养24 h后检测细胞活性、细胞氧化应激水平及心肌损伤标志物。结果 与Sham组比较，MCM组巨噬细胞上清液中一氧化氮水平显著增高（P=0.000 1）；MCM组心肌细胞活性氧（ROS）、脂质过氧化产物丙二醛（MDA）含量显著升高，而心肌细胞活性明显下降，心肌细胞释放的乳酸脱氢酶（LDH）及心肌型肌酸激酶同工酶明显升高（均P<0.05）。与MCM组比较，Tub A组ROS、MDA明显下降，细胞活性明显升高，LDH明显下降（均P<0.05）。结论 Tub A可以减轻LPS刺激巨噬细胞导致的心肌细胞损伤，其作用机制可能是通过降低氧化应激来完成的。

Tubastatin A通过降低氧化应激减轻脓毒症所致心肌损伤的体外研究

尤佳琪, 刘畅, 崇巍

中国医科大学附属第一医院急诊科, 沈阳 110001

收稿日期:2023-01-11出版日期:2023-07-30发布日期:2023-07-08
通讯作者:崇巍E-mail:wchong@cmu.edu.cn
作者简介:尤佳琪(1996-),女,硕士研究生.
基金资助:沈阳市重大科技创新研发计划（19-112-4-068）


关键词: Tubastatin A, 脓毒症, 心肌细胞, 氧化应激, 体外
Abstract: Objective To study the effects of Tubastatin A（Tub A）on oxidative stress damage caused by inflammatory cytokines produced by lipopolysaccharide（LPS）-stimulated macrophages（RAW264.7）. Methods Rat H9C2 myocardial cells were divided into three groups：the sham group，the MCM group，and the Tub A group. The sham group was cultured using the cell supernatant acquired from macrophages without LPS stimulation. The MCM group was cultured using the cell supernatant acquired from macrophages with LPS stimulation. The Tub A group was pretreated with Tub A and then cultured in the cell supernatant containing Tub A，which was acquired from macrophages with LPS stimulation. After culturing the three groups of myocardial cells for 24 h，various parameters including cell activity， cell oxidative stress levels，and the concentration of myocardial damage markers in the supernatant were determined. Results The concentration of nitric oxide in the cell supernatant of the MCM group was significantly higher than that in the sham group（P=0.000 1）. In the MCM group，cardiomyocytes displayed significantly elevated levels of reactive oxygen species（ROS）and the lipid peroxidation product malondialdehyde（MDA）compared to that of the sham group. Moreover，myocardial cell activity decreased significantly，and the levels of lactic acid dehydrogenase（LDH）and myocardial creatine kinase-MB（CK-MB）released by myocardial cells significantly increased in the MCM group（all P<0.05）. In contrast，the Tub A group demonstrated a significant decrease in ROS and MDA content，along with a significant increase in cell activity and a reduction in LDH release compared to that of the MCM group（all P<0.05）. Conclusion Tub A alleviates myocardial cell damage caused by LPS-stimulated macrophages，and the mechanism of action may be accomplished by reducing oxidative stress.
Key words: Tubastatin A, sepsis, myocardial cell, oxidative stress injury, in vitro
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