【摘要】 目的探讨蛋白酶体抑制剂对PC12细胞的作用以及用该药物制作帕金森病(PD)模型的可能性。方法用不同浓度蛋白酶体抑制剂PSI作用于PC12细胞24、48、72 h后,以MTT法检测细胞活性,荧光染色检测凋亡细胞百分率,HE染色观察细胞形态变化,透射电镜观察细胞超微结构变化。结果不同浓度PSI作用于PC12细胞24 h时,细胞存活率无变化;作用48~72 h时,1~20μmol/L PSI使细胞存活率分别降至47.03%~58.98%和19.58%~34.72%;凋亡细胞由1.15%升至5.27%。HE染色显示经PSI处理的PC12细胞胞浆内有嗜酸性包涵体出现,透射电镜下细胞呈凋亡的超微结构特点。结论PC12细胞蛋白酶体受抑模拟了PD的两大病理特点,蛋白酶体功能异常可能是PD的发病因素之一,短期抑制PC12细胞的蛋白酶体功能可作为PD的细胞模型。更多还原

【Abstract】 Objective To study the Parkinson model of PC12 cells induced by proteasomal inhibition(PSI).Methods The viability of PC12 cells was assayed by MTT,after incubation in different-concentrations of PSI for different periods(24,48 or 72 h);the apoptotic proportion was calculated after fluorescent stain;configuration of the cells were observed cytological and ultrastructural by HE stain and transmission electron microscopy.ResultsThe viability of PC12 cells was not influenced by incubation with PSI for 24 hours,but it was decreased to 47.03%-58.98% and 19.58%-34.72% by incubation with 1-20 μmol/L PSI for 48 and 72 h respectively.According to fluorescent stain observation,the proportion of apoptotic cell increased from 1.15% to 5.27%.Eosinophilic cytoplasmic inclusion was detected in PC12 cells treated with PSI after HE stain.Ultrastructural changes of apoptosis could be observed in some of the cells by transmission electron microscopy.Conclusions The two most important pathologic ultrastructural features of Parkinson disease can be induced in PC12 cells by treatment of proteasomal inhibitor PSI.Proteasomal dysfunction may be one of the pathogenetic factors of Parkinson disease and short-time inhibition of proteasome function can be used as a cell model of Parkinson disease.更多还原