中文摘要：

目的探讨18 ku转位蛋白TSPO选择性配体YL-IPA08对皮质酮诱导BV-2细胞凋亡的保护作用,并研究其可能的作用机制。方法选择性TSPO配体YL-IPA08 1-100 nmol·L（-1）和（或）TSPO拮抗剂PK11195 100 nmol·L（-1）预处理小胶质细胞系BV-2细胞2 h,加入皮质酮200μmol·L（-1）继续培养24 h,分别用流式细胞术检测细胞凋亡,CCK-8法检测细胞存活,Western蛋白质印迹法检测TSPO蛋白表达水平,ELISA法检测细胞培养上清中四氢孕酮的水平。结果与溶剂对照组相比,YL-IPA08 1-100 nmol·L（-1）与阳性化合物AC-5216一样能降低皮质酮处理的BV-2细胞的凋亡率（P〈0.01）,且100 nmol·L（-1）时作用最为显著,该作用能被PK11195 100 nmol·L（-1）所拮抗（P〈0.05）。细胞活性检测显示,YL-IPA08 100 nmol·L（-1）时能显著升高细胞活性（P〈0.01）,PK11195 100 nmol·L（-1）处理会拮抗该作用（P〈0.01）。Western蛋白质印迹和ELISA法结果显示,YL-IPA08 100 nmol·L（-1）时能显著增加皮质酮处理的BV-2细胞TSPO蛋白的表达（P〈0.05）并显著升高培养液中四氢孕酮的水平（P〈0.05）,PK11195 100 nmol·L（-1）显著逆转该现象,降低四氢孕酮的水平（P〈0.05）。结论 YL-IPA08显著抑制皮质酮诱导BV-2细胞的凋亡,表现出对小胶质细胞的保护作用,该作用与其增加TSPO蛋白的表达、升高四氢孕酮的水平密切相关。

英文摘要：

OBJECTIVE To investigate the protective effect of selective 18 ku translocator protein（TSPO） ligand YL-IPA08 on corticosterone（CORT）-induced apoptosis of BV-2 cel s and its potential mechanisms. METHODS BV-2 Cells were pretreated with selective TSPO ligand YL-IPA08 1-100 nmol·L（-1）and（or） TSPO antagonist PK11195 100 nmol·L-1for 2 h,and then co-incubated with CORT for another24 h. The apoptosis rate was measured by flow cytometry. CCK-8 kit was used to test BV-2 cell viability. The protein expression of TSPO was determined by Western blotting. The level of allopregnanolone was detected by ELISA kit. RESULTS In line with positive drug-AC-5216, the cell apoptosis rate decreased in YL-IPA08 1-100 nmol·L（-1）and CORT co-treatment groups（P0.01）, which was antagonized by PK11195 100 nmol·L（-1）treatment（P0.05）. Cell viability increased in YL-IPA08 100 nmol·L（-1）and CORT co-treatment groups（P0.01）, which was blocked by PK11195 100 nmol·L（-1）treatment（P0.01）.The expression of TSPO and the level of allopregnanolone（P0.01） were enhanced by YL-IPA08100 nmol·L-1pretreatment followed by CORT treatment. The enhancement of allopregnanolone level was blocked by PK11195 100 nmol·L（-1）treatment（P0.05）. CONCLUSION YL-IPA08 can protect BV-2cells from CORT induced apoptosis. The protective effect of YL-IPA08 may be conferred by the increasing level of TSPO expression and allopregnanolone.