【摘要】 目的建立简便有效的筛选系统,筛选脑源性神经营养因子(BDNF)样小分子化合物,用于探讨中枢神经系统神经损伤保护。方法依次利用多巴胺能SH-SY5y细胞、稳定转染BDNF受体基因trkB的NIH3T3/trkB细胞和正常生长的NIH3T3细胞组成BDNF样化合物筛选系统,以BDNF为阳性对照,通过试验样品对去血清致细胞凋亡的抵抗作用,确定其是否具有BDNF样活性。结果利用所建筛选系统筛选化合物400个,获得能够促进SH-SY5y细胞存活的化合物11个,同时能够相对特异抵抗去血清致NIH3T3/trkB细胞凋亡的BDNF样小分子2个。进一步实验表明该2个化合物对6-OHDA致SH-SY5y细胞损伤具有一定的保护作用。结论该工作为大规模筛选和深入研究BDNF样化合物的神经保护功能提供了模型和先导化合物基础。更多还原

【Abstract】 Aim To apply simple combined models to screen small molecule BDNF-like compounds for potential pharmacotherapy of central nerve degenerative diseases.Methods BDNF-like bioactivities were dentified with effects against apoptosis induced by serum withdrawal in turn in cultured human SH-SY5y cells,rat NIH3T3/trkB cells vs NIH3T3 cells,using MTT technique.Results More than 400 compounds were tested by using these methods.11 of them presented protective effects on apoptosis induced by serum withdrawal in SH-SY5y cells.2 of them also provided selective protection against apoptosis induced in NIH3T3/trkB cells versus in NIH3T3 cells,which were identified as BDNF-like compounds.Further study showed that these 2 compounds could withstand SH-SY5y cell injuries induced by 6-OHDA.Conclusion All the above studies provide a useful series of simple models for BDNF-like drug screen and some compound candidates for further study of neuroprotection.更多还原