6-羟基-1-氢-吲唑保护MPP^+诱导凋亡的SH-SY5Y细胞的机制  

The mechanism of 6-hydroxy-1H-indazole's neuroprotection from MPP^+-induced apoptosis of SH-SY5Y cells

作　　者：梁小凤[1] 朱雯婷 饶进军[1] 王文雅[1] 

机构地区：[1]南方医科大学药学院临床药理研究所,广州510515 [2]江西省新余市人民医院药剂科,新余338000

出　　处：《安徽医科大学学报》2015年第5期585-589,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金重点项目(编号:81030024);广东省自然科学基金(编号:S2012010009368);广东省教育部产学研结合项目(编号:2012B091100465)

摘　　要：目的研究6-羟基-1-氢-吲唑对1-甲基-4-苯基-吡啶离子(MPP+)诱导凋亡的SH-SY5Y细胞的保护作用机制。方法体外培养人神经母细胞瘤细胞SH-SY5Y,以200μmol/L MPP+诱导SH-SY5Y细胞凋亡建立体外帕金森病细胞模型。Western blot法分别检测200μmol/L MPP+和200μmol/L MPP+联合0.1μmol/L 6-羟基-1-氢-吲唑作用后SHSY5Y细胞内糖原合酶激酶3β(GSK-3β)、周期依赖性蛋白激酶5(CDK5)以及凋亡蛋白酶3(caspase-3)的活性。结果200μmol/L MPP+作用SH-SY5Y细胞8 h,GSK-3β、CDK5与caspase-3活性升高。200μmol/L MPP+联合0.1μmol/L 6-羟基-1-氢-吲唑作用SH-SY5Y细胞8 h,GSK-3β、CDK5与caspase-3的活性降低。结论 6-羟基-1-氢-吲唑对MPP+诱导凋亡的SH-SY5Y细胞的保护机制可能是抑制GSK-3β、CDK5和caspase-3的活性。Objective To investigate the mechanism of 6-hydroxy-1H-indazole’s neuroprotection from 1-methyl-4-phenylpyridinium（MPP ＋ ）-induced apoptosis of SH-SY5Y cells. Methods The model of Parkinson’s disease in＆amp;nbsp;vitro was built through SH-SY5Y cells’s exposure to 200 μmol/ L MPP ＋ . Cultured SH-SY5Y cells were respective-ly exposed to 200 μmol/ L MPP ＋ and 200 μmol/ L MPP ＋ combined 0. 1 μmol/ L 6-hydroxy-1H-indazole, then the variations of activity of glycogen synthase kinase-3β（GSK-3β）, cyclin dependent kinase 5（CDK5） and caspase-3 were determined by Western blot. Results 200 μmol/ L MPP ＋ increased the activity of GSK-3β, CDK5 and caspase-3 in SH-SY5Y cells. 200 μmol/ L MPP ^＋ combined 0. 1 μmol/ L 6-hydroxy-1H-indazole inhibited the activ-ity of GSK-3β, CDK5 and caspase-3 in SH-SY5Y cells. Conclusion 6-hydroxy-1H-indazole decreases the activity of GSK-3β, CDK5 and caspase-3 to protect SH-SY5Y cells from MPP ＋ -induced toxicity.

关 键 词：6-羟基-1-氢-吲唑 SH-SY5Y细胞 MPP^+ 糖原合酶激酶3Β 周期依赖性蛋白激酶5 凋亡蛋白酶3 

分 类 号：R962[医药卫生—药理学] R742.5[医药卫生—药学]