抗氧化干预对低氧低糖诱导血管平滑肌细胞自噬和铁死亡的影响

目的观察抗氧化干预对低氧低糖处理后血管平滑肌细胞(VSMC)自噬和铁死亡发生的影响及其与血管功能的关系。方法采用低氧低糖培养的VSMC和创伤失血休克大鼠模型,观察抗氧化剂依达拉奉(EDA)对低氧低糖处理后VSMC中自噬标志物、铁死亡标志物及细胞反应性的影响,并观察EDA对休克大鼠血管反应性的影响。结果低氧低糖处理后VSMC中自噬标志物LC3-Ⅱ/LC3-Ⅰ比值升高、p62蛋白表达水平降低,提示自噬水平升高。低氧低糖也导致了VSMC铁死亡的发生,铁死亡标志物谷胱甘肽过氧化物酶4(GPx4)和溶质载体家族7成员11(SLC7A11)的表达水平降低。抗氧化剂EDA处理可抑制细胞自噬水平的升高,使LC3-Ⅱ/LC3-Ⅰ比值降低、p62蛋白表达水平升高;但EDA对GPx4和SLC7A11表达的影响无统计学意义。同时,低氧低糖处理后细胞收缩反应性明显降低,EDA处理可恢复低氧低糖细胞的收缩反应性。在创伤失血休克大鼠中,血管收缩反应性明显降低,抗氧化剂EDA处理可提高休克大鼠的血管收缩反应性。结论抗氧化干预可抑制低氧低糖诱导的VSMC自噬,改善低氧细胞和休克血管的收缩功能。

Effects of antioxidative intervention on hypoxia/hypoglycemia-induced autophagy and ferroptosis in vascular smooth muscle cells

Objective To investigate the effects of antioxidative intervention on autophagy and ferroptosis in vascular smooth muscle cells(VSMC)after hypoxia/hypoglycemia treatment and its relationship with vascular function.Methods VSMC cultured with hypoxia/hypoglycemia and traumatic hemorrhagic shock rats model were used to observe the effects of antioxidant edaravone(EDA)on autophagy markers,ferroptosis markers and the cellular reactivity in VSMC after hypoxia/hypoglycemia treatment,and to observe the effecst of EDA on the vascular reactivity of shock rats.Results After hypoxia/hypoglycemia treatment,the ratio of autophagy markers LC3-Ⅱ/LC3-Ⅰin VSMC increased,and the expression level of p62 protein decreased,which suggested that the autophagy level increased.Hypoxia/hypoglycemia also caused ferroptosis in VSMC,and the expression levels of ferroptosis markers glutathione peroxidase 4(GPx4)and solute carrier family 7 member 11(SLC7A11)decreased.Antioxidant EDA treatment could inhibit the increase of autophagy level,reduce the ratio of LC3-Ⅱ/LC3-Ⅰand increase the expression level of p62 protein;however,the effect of EDA on the expression of GPx4 and SLC7A11 was not statistically significant.Meanwhile,the cellular contraction reactivity was significantly decreased after hypoxia/hypoglycemia treatment,and EDA treatment could restore the contraction reactivity of hypoxia/hypoglycemia cells.In the traumatic hemorrhagic shock rats,the vascular contraction reactivity was significantly reduced,and the antioxidant EDA treatment could increase the vascular contraction reactivity of the shock rats.Conclusion Antioxidative intervention can inhibit hypoxia/hypoglycemia-induced autophagy in VSMC,and improve the contraction function of hypoxic cells and shock vessels.