中国临床药理学杂志2025，Vol.41Issue(3)：335-339,5.DOI:10.13699/j.cnki.1001-6821.2025.03.008
PX-478改善辐照诱导的心肌细胞凋亡的作用
PX-478 ameliorates irradiation-induced apoptosis of cardiomyocytes
摘要
Abstract
Objective To investigate the efficacy of the hypoxia-inducible factor-1α(HIF-1α)inhibitor PX-478 in improving radiation-induced apoptosis in cardiomyocytes and to elucidate its molecular mechanisms.Methods H9c2 cells were divided into blank group,model group,experimental-L group and experimental-H group.The experimental-L,-H groups were cultured with PX-478 at concentrations of 5 and 10 mol·L-1,respectively,while the other groups were cultured in normal medium.After 24 h of culture,all groups except the blank group were irradiated with 6 Gy X-rays to establish a model of radiation-induced cardiac injury and were subsequently cultured for another 24 h.Cell viability was assessed using the cell counting kit-8 assay;relative protein expression levels were determined by Western blotting;and apoptosis was detected using Annexin V/PI flow cytometry.Results The relative expression levels of HIF-1 α protein in the blank group,model group,experimental-L group and experimental-H group were 0.89±0.01,1.05±0.01,0.64±0.02 and 0.52±0.02;the relative expression levels of aquaporin-1(AQP1)protein were 0.79±0.02,0.94±0.02,0.74±0.01 and 0.59±0.01;AQP4 protein levels were 0.89±0.01,1.03±0.01,0.68±0.01 and 0.50±0.01;B-cell lymphoma-2(Bcl-2)protein levels were 0.78±0.02,0.58±0.02,1.00±0.03 and 0.82±0.03;Bcl-2-associated X protein(Bax)levels were 0.66±0.01,0.96±0.01,0.77±0.01 and 0.27±0.03;Caspase-3 levels were 0.83±0.01,1.10±0.01,0.71±0.02 and 0.30±0.01;the apoptosis rates were(4.05±0.60)％,(17.82±0.63)％,(9.35±0.41)％and(9.07±0.57)％,respectively.The above indicators in the blank,experimental-L,experimental-H groups showed statistically significant differences compared to the model group(all P＜0.05).Conclusion PX-478 can improve radiation-induced cardiomyocyte edema and reduce apoptosis by inhibiting the abnormal activation of the HIF-1 α/AQPs axis in H9c2 cells after irradiation,thereby regulating fluid metabolism.关键词
PX-478/辐射/放射性心脏损伤/缺氧诱导因子-1α/水通道蛋白1/水通道蛋白4/凋亡Key words
PX-478/radiation/radiation-induced heart disease/hypoxia inducible factor-1α/aquaporin 1/aquaporin 4/apoptosis分类
医药卫生引用本文复制引用
李启杨,张尚祖,李洋洋,杨更强,张利英..PX-478改善辐照诱导的心肌细胞凋亡的作用[J].中国临床药理学杂志,2025,41(3):335-339,5.基金项目
国家自然科学基金资助项目(82260882) （82260882）
中国博士后科学基金资助项目(2021M693794) （2021M693794）
