Hypoxia-inducible factor-1α relieves mitochondrial damage in hypoxic vascular endothelial cells / 中华创伤骨科杂志

ABSTRACT

Objective To investigate the protective mechanism of hypoxia-inducible factor-1α (HIF-1α) in vascular endothelial cells under hypoxia.Methods 1.After a hemorrhagic shock model was established in mice,the vascular endothelial cells were sorted in a shock group (n =3) and a sham operation group (n =3) for RNA-sequencing to analyze the main differential molecules.2.The expression of HIF-1α and glucose transporter-1 (GLUT1) was measured in human umbilical vein endothelial cells (HUVECs) and the mitochondrial membrane potentials were detected in a control group (normal culture,n =3) and a hypoxia group (hypoxia culture for 6 h,n =3).3.The HUVECs cells were transfected with HIF-1α siRNA for 48 h to interfere with HIF-1 α expression,and the control group(n =3) was transfected with control siRNA.The expression of HIF-1α was detected to determine the interference effect.The mRNA and protein expression of GLUT1 was detected in the interference and the control groups after 6 h of hypoxia culture.The mitochondrial membrane potential was detected by fluorescent probe method.Results 1.The transcriptome sequencing in the vascular endothelial cells in the shock and sham operation groups indicated 25 genes with significant differences.The HIF-1 α expression was significantly increased in the shock group (111.70 ± 15.97) than in the sham operation group (53.49 ± 3.26) (P =0.023).2.The expression of HIF-1 α and GLUT1 in the HUVECs cells was significantly increased in the hypoxia group compared with the control group (P ＜ 0.05).The mitochondrial membrane potential was significantly lower in the hypoxia group (0.781 ± 0.023) than in the control group (1.177 ± 0.062) (P ＜ 0.05),indicating aggravated injury.3.There was no significant difference in the mitochondrial membrane potential between the interference group (1.011 ± 0.076) and the control group (1.151 ± 0.031) (P ＞ 0.05).However,after hypoxia culture for 6 h,there was a significant difference in the mitochondrial membrane potential between the interference group (0.514 ± 0.018) and the control group (0.769 ± 0.044) (P ＜ 0.05),also indicating aggravated damage.Conclusions The expression of HIF-1 α may be significantly increased in hemorrhagic shock.In HUVECs under hypoxia,HIF-1 α may up-regulate the expression of GLUT1,promote glucose transport,improve mitochondrial damage and protect vascular endothelial cells.Thus,targeting HIF-1 α may contribute to the treatment of hemorrhagic shock.