中国病理生理杂志2026，Vol.42Issue(1)：80-87,8.DOI:10.3969/j.issn.1000-4718.2026.01.010
线粒体HIGD1A表达受抑加重多柔比星引起的H9c2心肌细胞焦亡
Repressed mitochondrial HIGD1A expression aggravates doxorubicin-in-duced pyroptosis of rat H9c2 cardiomyocytes
摘要
Abstract
AIM:Doxorubicin(DOX)-induced heart failure is a serious complication in tumor chemotherapy,but the underlying mechanisms are not well clarified.This study aimed to investigate whether and how the mitochondrial hypoxia-induced gene domain family member 1A(HIGD1A)plays a role in DOX-induced cardiomyocyte injury especially pyroptosis.METHODS:H9c2 cardiomyocytes were cultured and treated with DOX for 24 h to induce cardiomyocyte inju-ry.The cells were divided into seven groups according to the treatment(s):control,DOX,siNC,Higd1a siRNA(si-Higd1a),siNC+DOX,si Higd1a+DOX,and si Higd1a+DOX+MCC950[a nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inhibitor].DHE staining was performed to measure intracellular reactive oxygen species(ROS),TMRE staining was used to evaluate mitochondrial function,Western blot was employed to detect the expression of pyroptosis-related proteins,and lactate dehydrogenase(LDH)release was detected to evaluate cardiomyocyte injury.RESULTS:DOX markedly repressed the expression of HIGD1A both at the mRNA and the protein levels(P<0.05),and significantly decreased the viability of H9c2 cardiomyocytes(P<0.01),compared to the control group.Silencing of Higd1a by siRNA exacerbated DOX-induced ROS generation,declined mitochondrial membrane potential(P<0.01),in-creased the expressions of pyroptosis markers including NLRP3,gasdermin D cleaved fragment,cleaved caspase-1 and in-terleukin-18(P<0.01),and promoted LDH release(P<0.01).Treatment with MCC950 to inhibit NLRP3 partially re-versed cardiomyocyte pyroptosis caused by Higd1a silencing(P<0.05).CONCLUSION:Repressed HIGD1A expres-sion is responsible for DOX-induced mitochondrial dysfunction and pyroptosis of H9c2 cardiomyocytes.Inhibiting NLRP3 by MCC950 partially reverses DOX-induced HIGD1A downregulation and cardiomyocyte pyroptosis.关键词
缺氧诱导的基因结构域家族成员1A/多柔比星/心肌细胞/细胞焦亡Key words
hypoxia-induced gene domain family member 1A/doxorubicin/cardiomyocytes/pyroptosis分类
医药卫生引用本文复制引用
贺忠梅,杨靖宇,钟祺,裴旭婷,高丽娟,曹济民..线粒体HIGD1A表达受抑加重多柔比星引起的H9c2心肌细胞焦亡[J].中国病理生理杂志,2026,42(1):80-87,8.基金项目
山西省自然科学基金面上项目(No.202303021211110) （No.202303021211110）
山西省回国留学人员科研资助项目(No.2020-078) （No.2020-078）
