SB239063,新一代p38丝裂原活化蛋白激酶抑制剂在缺氧缺糖所致SHSY5Y细胞损伤中的作用

Role of SB239063,the new p38 mitogen-activated protein kinase inhibitor,on the cell damage of SHSY5Y neuronal cells from oxygen-glucose deprivation

目的探讨SB239063,新一代p38丝裂原活化蛋白激酶抑制剂(p38MAPK)在缺氧缺糖(OGD)所致SHSY5Y细胞损伤中的作用。方法体外培养SHSY5Y神经母细胞瘤株,以缺氧缺糖、SB239063(10μmol/L)处理,以MTT检测SHSY5Y细胞活性,以Westernblot方法检测p38MAPK活性,应用HEt和fluo-3/AM的荧光强度测定OGD后SHSY5Y细胞超氧化物阴离子和钙离子的浓度。结果SB239063能提高OGD后SHSY5Y细胞的活性(P<0.01),降低OGD后p38MAPK活性(P<0.05),HEt(P<0.05)和fluo-3/AM荧光强度(P<0.01)。结论SB239063通过抑制p38MAPK的激活,降低细胞内超氧阴离子的浓度,进而抑制细胞内钙超载,从而达到保护SHSY5Y细胞对抗OGD的细胞损害的作用。

Objective To investigate the neuroprotective effect of SB239063,the new p38 mitogen-activated protein kinase （MAPK） inhibitor on SHSYSY neuronal cells against oxygen-glucose deprivation （OGD）, and the mechanisms of the neuroprotective effect. Methods SHSYSY neuroblastoma cells were exposed to OGD with or without SB239063 （ 10μmol/L） , cell viability was measured by the MTT assay, activity of p38MAPK was measured by western blot, intracellu- lar concentration of superoxide anion and calcium were evaluated via the fluorescence intensity of HEt and fluo-3/AM. Resuits Compared with the OGD group, the MTr value was elevated significantly in the SB239063 group （P 〈 0.01 ）, the activity of p38MAPK decreased significantly in the SB239063 group （ P 〈 0.01 ）, the fluorescence intensity of HEt （ P 〈 0.05） and fluo-3/AM （P 〈 0.01 ） decreased significantly in the SB239063 group. Conclusion SB239063 protects SHSY5Y neuronal cells against OGD by inhibiting the activity of p38MAPK,then reducing the intracellular concentration of superoxide anion and calcium.