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纳米氧化铈在阿霉素诱导心脏毒性中的作用及其对P53基因表达的影响
引用本文:李俊奇,韩轩茂,蔺雪峰,袁敏. 纳米氧化铈在阿霉素诱导心脏毒性中的作用及其对P53基因表达的影响[J]. 中国现代医生, 2024, 62(5): 67-72
作者姓名:李俊奇  韩轩茂  蔺雪峰  袁敏
作者单位:内蒙古科技大学包头医学院研究生院,内蒙古包头 014000;内蒙古科技大学包头医学院第一附属医院心内科一病区,内蒙古包头 014000
基金项目:内蒙古自治区自然科学基金项目(2020MS08068)
摘    要:目的 研究纳米氧化铈在阿霉素心脏毒性损伤中的作用及其对P53基因表达的影响,探讨纳米氧化铈对阿霉素心脏毒性损伤的作用机制。方法 培养H9C2心肌细胞,随机分为5组:对照组、模型组(1μmol/L阿霉素)、纳米氧化铈组(10μg/ml纳米氧化铈)、实验组(1μmol/L阿霉素+10μg/ml纳米氧化铈)、阳性对照组(1μmol/L阿霉素+10μmol/L右丙亚胺)。建立阿霉素心脏毒性损伤模型,CCK-8法检测心肌细胞的存活率;生化法检测心肌细胞内乳酸脱氢酶(lactic dehydrogenase,LDH)、丙二醛(malondialdehyde,MDA)的含量;流式细胞仪检测心肌细胞内活性氧(reactive oxygen,ROS)水平及细胞凋亡率;Western blot检测心肌细胞中Bax、Bcl-2及P53蛋白的表达。结果 与对照组相比,模型组的细胞存活率下降,细胞LDH、MDA含量上升,细胞内ROS水平和凋亡率增加,Bax和P53蛋白表达量升高,Bcl-2蛋白表达量下降,且Bcl-2/Bax比值下降(均P<0.001);与模型组相比,实验组细胞存活率上升,细胞LDH、MD...

关 键 词:纳米氧化铈  阿霉素  心脏毒性  P53基因  细胞凋亡

Role of cerium oxide nanoparticles in doxorubicin-induced cardiotoxicity and its effect on P53 gene expression
Abstract:Objective To study the effect of nano-ceria on doxorubicin-induced cardiotoxic injury and its effect on P53 gene expression, and to explore the mechanism of nano-ceria on doxorubicin-induced cardiotoxic injury. Methods H9C2 myocardial cells were cultured and randomly divided into five groups: control group, model group (1μmol/L adriamycin), nano-cerium oxide group (10μg/ml nano-cerium oxide), experimental group (1μmol/L adriamycin +10μg/ml nano-cerium oxide), and positive control group (1μmol/L adriamycin+10μmol/L dexperimine). The adriamycin induced cardiotoxicity model was established, and the viability of myocardial cells was measured by CCK-8 method. The contents of lactate dehydrogenase (LDH) and malondialdehyde (MDA) in myocardial cells were detected by biochemical method. The levels of reactive oxygen (ROS) and the apoptosis rate in myocardial cells were detected by flow cytometry. The expressions of Bax, Bcl-2 and P53 proteins in myocardial cells were detected by Western blot. Results Compared with the control group, the cell viability was decreased in the model group, the cell LDH and MDA contents were increased, the intracellular ROS level and apoptosis rate were increased, the expressions of Bax and P53 proteins were increased, and the expression of Bcl-2 protein was decreased, and the ratio of Bcl-2/Bax was decreased (all P<0.001). Compared with the model group, the experimental group showed increased cell viability, decreased cell LDH and MDA contents, decreased cell ROS content and apoptosis rate, decreased Bax and P53 protein expressions, and increased Bcl-2 protein expression, and the Bcl-2/Bax ratio was increased (all P<0.001). Conclusion Ceria nanoparticles can effectively prevent adriamycin-induced cardiotoxic injury, and its effect may be related to the down-regulation of P53 gene to inhibit cardiomyocyte apoptosis.
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