不同价态锰对神经细胞的毒性比较以及硒的保护作用

Neural Toxicity Induced by Divalent and Tetravalent Forms of Manganese and its Protection by Selenium

目的研究不同价态锰化合物对神经母细胞瘤细胞(SH-SY5Y)DNA损伤作用、细胞凋亡和细胞周期的影响,以及抗氧化剂硒的保护作用,从而探讨锰的神经毒作用机制。方法将培养的SH-SY5Y细胞随机分为染毒的二价锰和三价锰化合物(0.5 mmol/L)组、空白对照组、硒干预组。培养24 h后应用单细胞凝胶电泳检测细胞DNA链断裂情况。48 h后用流式细胞仪测定细胞凋亡率、细胞周期分布。结果三价锰组DNA损伤程度比二价锰组严重。二价锰和三价锰组均出现亚二倍体的凋亡峰;细胞周期分布也发生改变,与对照组相比S期细胞明显增多,差异有统计学意义(P<0.01);三价锰比二价锰更易引起细胞凋亡(P<0.01)和细胞周期变化(P<0.05)。硒可降低锰化合物引起的细胞DNA损伤、凋亡率和细胞周期中S期细胞数。结论不同价态锰对神经细胞均有损伤作用,且三价锰大于二价锰。硒对锰致细胞DNA损伤、凋亡和细胞周期改变有一定的保护作用,提示氧化应激可能参与了锰的毒作用。

Objective The neural toxicity induced by manganese with different valence was compared, and the protective effectsof selenium was investigated. Methods The SH-SYSY cells were divided into the following groups： control; Mn^2＋ ; Mn^3＋ ; Selenium; Mn^2＋ ＋ Selenium; Mn^3＋ ＋ Selenium. The degree of DNA strand break was determined using a Single Cell Gel Electrophoresis method. Cell apoptosis and cell cycle distribution were determined by flow cytometry. Results Mn^3 ＋ induced more DNA strand break, apoptosis and S phase accumulation than Mn^2＋ . The neural toxicity induced by either Mn^3＋ or Mn^2＋ was reduced by selenium. Conclusion Mn^3 ＋ exhibits stronger neural toxicity than Mn^2 ＋ . Selenium may be a potential agent to protect neurons from Mn-induced damage.