虾青素缓解Tau蛋白过度磷酸化减轻视神经放射性损伤的分子生物学机制探讨

Molecular biological mechanisms of astaxanthin in alleviating Tau hyperphosphorylation and reducing optic nerve radiation damage

目的分析视神经放射性损伤的分子生物学机制及虾青素对Tau蛋白过度磷酸化减轻效果。方法选取64例离体培养鼠视网膜神经节细胞株RGC-5培养的神经元,30 Gyγ射线电离辐射,随机选择64个细胞培养小室,根据有无虾青素滴加分为虾青素标准品组及无虾青素标准品组各32个,观察两组照射后12 h、24 h、48 h、1周后Tau蛋白激酶、GSK-3β蛋白、PP-2A蛋白表达差异。结果同组不同时间比较可见虾青素标准品组照射后随时间增长,Tau蛋白激酶、GSK-3β蛋白有所下降,PP-2A蛋白表达有所上升,这种变化在无虾青素标准品组表现不明显(P>0.05),同时间组间比较照射后不同时间虾青素标准品组Tau蛋白激酶、GSK-3β蛋白表达低于无虾青素标准品组,而PP-2A蛋白表达高于无虾青素标准品组,数据经统计学处理,差异均有统计学意义(P<0.05)。结论虾青素能够有效降低GSK-3β蛋白的表达及提高PP-2A蛋白表达,降低γ射线电离辐射致Tau蛋白过度磷酸化,从而可能对抑制Tau蛋白过度磷酸化而预防电离辐射对视神经的损伤。

Objective To analyze the molecular biological mechanisms of optic nerve radiation damage and the effect of astaxanthin in alleviating Tau hyperphosphorylation. Methods Sixty-four cases of cultured neurons from in vitro cultured rat retinal ganglion cell line RGC-5 underwent γ-ray ionizing radiation(30 Gy). Then 64 cell culture chambers were randomly selected and divided into astaxanthin group(n=32) and non-astaxanthin group(n=32) based on the presence or absence of astaxanthin. 12 h, 24 h, 48 h, 1 week after irradiation, the expression of Tau protein kinase,GSK-3β protein, PP-2A protein were observed and compared between the two groups. Results In astaxanthin group,the expression of Tau protein kinase, GSK-3β protein showed a decreasing trend 12 h, 24 h, 48 h, 1 week after irradiation, while the expression of PP-2A showed an increasing trend. This change was not significant in non-astaxanthin group(P>0.05). At the same time point, the expression of Tau protein kinase, GSK-3β protein were significantly lower in astaxanthin group than non-astaxanthin group, while the expression of PP-2A protein was significantly higher in astaxanthin group than non-astaxanthin group(P<0.05). Conclusion Astaxanthin can effectively reduce the expression of GSK-3β protein and increase the expression of PP-2A protein, alleviate Tau hyperphosphorylation induced by γ-ray ionizing radiation, and hence reduce the optic nerve radiation damage by inhibiting the overexpression of Tau protein.