IGF-1R/PI3K信号通路介导胰岛素样生长因子-1抗MPP+诱导多巴胺能神经元损伤的作用机制研究  

Mechanism of IGF-1R/PI3-K signaling pathway in neuroprotective effect of IGF-1 against MPP+-induced dopaminergic neuron injury

作　　者：原昕 赵梦佳 张欣 袁良杰 YUAN Xin;ZHAO Mengjia;ZHANG Xin;YUAN Liangjie(School of Basic Medical Sciences,Shandong First Medical University(Shandong Academy of Medical Sciences),Taian,Shandong 271000,China)

机构地区：[1]山东第一医科大学(山东省医学科学院)基础医学院,山东泰安271000

出　　处：《中国医学工程》2020年第10期15-18,共4页China Medical Engineering

基　　金：国家级大学生创业创新训练项目(201810439105)。

摘　　要：目的观察不同浓度的胰岛素样生长因子-1(IGF-1)对1-甲基-4-苯基吡啶离子(MPP+)诱导的多巴胺能神经元细胞系SH-SY5Y细胞损伤的保护作用、胰岛素样生长因子-1受体(IGF-1R)阻断剂和磷脂酰肌醇-3-激酶(PI3K)阻断剂LY294002的阻断效应。方法体外培养人神经母细胞瘤SH-SY5Y细胞,应用不同浓度的IGF-1(25、50及100 ng/mL)预处理细胞24 h,然后与MPP+(1 mM)共同处理细胞24 h;提前1h加入JB-1(1μg/mL)或LY294002(5μM),然后加入IGF-1预保护细胞24 h,与MPP+共同处理细胞24 h。应用Western blotting检测凋亡因子Bax和Bcl-2的蛋白变化,观察IGF-1的抗凋亡作用及阻断剂对IGF-1神经保护作用的阻断效应。结果MPP+处理组与对照组比较,Bax蛋白表达升高,而Bcl-2蛋白表达降低(P<0.05)。不同浓度的IGF-1与MPP+处理组比较,Bax蛋白表达降低,而Bcl-2蛋白表达升高(P<0.05)。JB-1或LY294002能够阻断IGF-1的该作用(P<0.05)。结论不同浓度的IGF-1能够对抗MPP+诱导的SH-SY5Y细胞凋亡,该作用与IGF-1R/PI3K信号通路有关。【Objective】To observe the neuroprotective effect of different concentrations insulin-like growth factor-1(IGF-1)against 1-methy-4-phenylpyridinium(MPP+)-induced SH-SY5Y cell injury and the blocking effect of insulin-like growth factor-1 receptor(IGF-1R)antagonist JB-1 and the PI3-K antagonist LY294002.【Methods】Cells were pretreated with different dosages of IGF-1(25 ng/mL,50 ng/mL,100 ng/mL)for 24 h,then co-treated with MPP+(1 mM)for another 24 h.For antagonist treatment,cells were pretreated with JB-1(1μg/mL)or LY294002(5μM)for 1 h before IGF-1 treatment.The protein expression of Bax and Bcl-2 were detected by western blot in order to clarify the neuroprotective effect of IGF-1 and the blocking effect of antagonist.【Results】Compared with control group,MPP+treatment dramatically up-regulated the protein expression of Bax and downregulated the protein expression of Bcl-2.Compared with MPP+group,Bax protein expression was significantly down-regulated and Bcl-2 protein expression was significantly up-regulated in different doses of IGF-1 treatment group.JB-1 and LY294002 could significantly block the effect of IGF-1.【Conclusion】Different concentration of IGF-1 could protect against MPP+-induced SHSY5Y cell injury through IGF-1R/PI3-K signaling pathway.

关 键 词：帕金森病 胰岛素样生长因子结合蛋白质1 实验室技术和方法 研究 

分 类 号：R34[医药卫生—基础医学]