黄芪甲苷通过HIF-1α信号通路调节糖代谢减轻放射性心肌细胞凋亡OA

Objective:To investigate the effects of astragaloside Ⅳ on glucose metabolism and apoptosis in a cellu-lar model of radiation-induced heart disease(RIHD).Methods:A HL-1 cardiomyocyte RIHD model was established u-sing 6 Gy X-ray irradiation.The experiment was divided into a model control group and groups treated with 20,40,and 80 μmol/L of Astragaloside Ⅳ;a blank control group was also included.Cell viability was assessed using the CCK-8 as-say,ATP and lactate levels were measured by colorimetric methods,and apoptosis was analyzed by flow cytometry.Mito-chondrial ultrastructure was observed using transmission electron microscopy,and mitochondrial membrane potential was assessed by JC-10 staining.Western blot was used to detect the expression levels of HIF-1α and glucose metabolism-re-lated proteins(HK2,PFKM,PKM2,PDK4,LDHA).Results:Compared with the blank control group,the model control group exhibited significantly decreased cell viability(P＜0.01),reduced ATP content,increased lactate levels(P＜0.01),marked mitochondrial damage,decreased mitochondrial membrane potential,significantly increased apoptosis(P＜0.01),and upregulated expression of HIF-1α,HK2,PFKM,PKM2,PDK4,and LDHA(P＜0.01).Compared with the model control group,all astragaloside Ⅳ groups showed significantly increased cell viability,elevated ATP content,re-duced lactate levels,alleviated mitochondrial damage,enhanced mitochondrial membrane potential,decreased apoptosis,and downregulated expression of HIF-1α,HK2,PFKM,PKM2,PDK4,and LDHA(P＜0.01).Conclusion:Astragaloside Ⅳ alleviates radiation-induced cardiomyocyte apoptosis by inhibiting HIF-1α-mediated glycolytic reprogramming and re-storing mitochondrial energy metabolism homeostasis.