马钱子复合生物碱成分抑制成年大鼠海马神经前体细胞的分裂作用

Strychnos alkaloids inhibit the proliferation of adult rat neuroprogenitor cells

目的探讨马钱子复合生物碱成分对成年大鼠海马神经前体细胞增殖的影响。方法提取马钱子生物碱,分离去除其中的士的宁和马钱子碱,制备马钱子复合生物碱成分。分别在HEK293和PC12细胞系上,采用MTT法观察马钱子复合生物碱成分对细胞存活的影响。然后在培养的成年大鼠海马神经前体细胞上,采用BrdU免疫荧光技术,研究不同浓度的马钱子复合生物碱成分对成年大鼠海马神经前体细胞增殖的影响。结果马钱子复合生物碱成分对HEK293细胞的存活无明显抑制作用,当其浓度>0.5mg/ml时,对HEK293细胞产生毒性作用(P<0.0001),但在PC12细胞中,马钱子复合生物碱成分在5μg/ml的浓度下即可明显抑制PC12的存活(P<0.0001)。在培养的成年大鼠海马神经前体细胞上,50μg/ml马钱子复合生物碱成分能够显著减少BrdU阳性细胞的数量(P<0.01),当浓度增加到100μg/ml时则能够产生明显的细胞毒性(P<0.001)。结论马钱子复合生物碱成分能够显著抑制PC12细胞的存活及成年大鼠海马神经前体细胞的分裂,并且这种抑制作用可能具有细胞选择性。

Objective To study the effects of strychnos alkaloids on the proliferation of adult rat neuroprogenitor cells. Methods Strychnos alkaloids flee of strychnine and brucine were extracted from Strychnos nux vomica, and the effects of Strychnos alkaloids on the survival of HEK293 and PC12 cells were evaluated using MTT assay. In vitro cultured adult rat neuroprogenitor cells isolated from the hippocampus were treated with different concentrations of Strychnos alkaloids for 2 days, and the cell proliferation was assessed using BrdU incorporation assay. Results At the concentration above 0.5 mg/ml, Strychnos alkaloids produced toxic effect against HEK293 cells （P〈0.0001）, while for PC12 cells, Strychnos alkaloids inhibited the cell survival at the concentration as low as 5 μg/ml （P〈0.0001）. After 2 days of exposure to 50 μg/ml Strychnos alkaloids, the neuroprogenitor cells showed significantly decreased number of BrdU-positive cells （P〈0.01）, but the total cell number remained stable when compared with that of the control cells （P〉0.05）, whereas at the concentration of 100 μg/ml, Strychnos alkaloids produced obvious cytotoxicity against the neuroprogenitor cells. Conclusion Strychnos alkaloids can significantly inhibit the proliferation of adult rat neuroprogenitor cells, and this effect is probably selective, suggesting the potential of Strychnos alkaloids as a new drug for treatment ofneurocytoma.