乙酸钠对氧糖剥夺皮质神经元损伤的作用及HIF-1α表达的影响

EFFECT OF SODIUM ACETATE ON CORTICAL NEURONAL INJURY CAUSED BY OXYGEN-GLUCOSE DEPRIVATION AND ITS INFLUENCE ON THE EXPRESSION OF HYPOXIA-INDUCIBLE FACTOR 1α

目的探讨乙酸钠(NaAc)对氧糖剥夺(OGD)损伤后皮质神经元的作用及低氧诱导因子-1α(HIF-1α)表达的影响。方法将OGD处理的皮质神经元作为脑缺血模型,采用细胞存活实验(CCK-8)、乳酸脱氢酶(LDH)释放实验检测NaAc处理后的神经元存活情况,Western blot方法检测OGD损伤后、NaAc处理后神经元中HIF-1α蛋白表达;应用二甲基草酰甘氨酸(DMOG)、HIF-1α抑制剂(LW6)分别激动和抑制HIF-1α,观察NaAc是否通过抑制HIF-1α发挥神经保护作用。采用2,3,5-氯化三苯基四氮唑(TTC)染色观察NaAc处理后大鼠脑组织梗死体积。结果TTC结果显示,NaAc处理可以减轻脑梗死体积(F=107.20,P<0.05)。体内细胞存活实验和LDH释放实验显示,NaAc可以减轻OGD对神经元的损伤(F=98.80、72.62,P<0.05),NaAc通过抑制HIF-1α表达促进神经元存活(F=43.57、97.52,P<0.05)。Western blot结果显示,NaAc可抑制正常神经元中HIF-1α蛋白的表达(t=7.84,P<0.05),OGD损伤后神经元HIF-1α蛋白表达增加(t=9.96,P<0.05),NaAc可抑制OGD损伤后神经元HIF-1α蛋白表达(F=74.74,P<0.05)。结论OGD损伤后,补充NaAc可通过抑制HIF-1α蛋白表达发挥神经保护作用。

Objective To investigate the effect of sodium acetate(NaAc)on cortical neurons after oxygen-glucose deprivation(OGD)injury and its influence on the expression of hypoxia-inducible factor 1α(HIF-1α).Methods Cortical neurons treated with OGD were established as a model of cerebral ischemia.CCK-8 assay and lactate dehydrogenase(LDH)release assay were used to measure the viability of neurons treated with NaAc;Western blot was used to measure the protein expression of HIF-1αin neurons after OGD injury and NaAc treatment;HIF-1αwas stimulated by dimethyloxalylglycine and inhibited by an HIF-1αinhibitor(LW6)to observe whether NaAc exerts a neuroprotective effect by inhibiting HIF-1α.The 2,3,5-triphenyltetrazolium chloride(TTC)staining was used to observe cerebral infarct volume of the rats treated with NaAc.Results TTC staining showed that NaAc treatment reduced cerebral infarct volume(F=107.20,P<0.05).In vivo cell survival test and LDH release assay showed that NaAc alleviated neuronal injury caused by OGD(F=98.80,72.62;P<0.05)and promoted the survival of neurons by inhibiting HIF-1αexpression(F=43.57,97.52;P<0.05).Western blot showed that NaAc inhibited the protein expression of HIF-1αin normal neurons(t=7.84,P<0.05),and there was a significant increase in the protein expression of HIF-1αin neurons after OGD injury(t=9.96,P<0.05),while NaAc inhibited the protein expression of HIF-1αin neurons after OGD injury(F=74.74,P<0.05).Conclusion NaAc supplementation exerts a neuroprotective effect after OGD injury by inhibiting the protein expression of HIF-1α.