中文摘要：

目的探讨阿魏酸（FA）对脂多糖（LPS）诱导的PC12细胞和大鼠海马神经元损伤的保护作用,并探讨其可能的作用机制。方法体外实验：FA 2.5～40μmol·L-1与PC12细胞预处理12 h,加入LPS 0.15 g·L-1继续培养8 h,采用CCK-8法检测细胞活力;ELISA法检测细胞培养上清中肿瘤坏死因子α（TNF-α）和白细胞介素1β（IL-1β）的释放;激光共聚焦显微镜检测细胞骨架蛋白F肌动蛋白的表达。体内实验：FA25,50和100 mg·kg-1ip给予SD大鼠,每天1次,连续35 d。给药第29天时ip给予LPS 0.2 mg·kg-1,每天1次,连续7d,运用免疫组织化学法观察大鼠海马神经元磷酸二酯酶4B（PDE4B）蛋白表达的变化;Western蛋白质印迹法检测cAMP反应元件结合蛋白（CREB）和磷酸化CREB（p-CREB）表达。结果体内实验：与LPS组细胞比较,FA 10,20和40μmol·L-1预处理组细胞活力明显升高（P〈0.05）,炎性因子TNF-α和IL-1β的释放显著减少（P〈0.05）,细胞骨架蛋白F肌动蛋白的分布和结构明显改善。体内实验：HE染色结果显示,预先给予FA 50和100 mg·kg-1可以减轻LPS诱导的大鼠海马神经元损伤;免疫组织化学实验结果显示,FA 50和100 mg·kg-1能够显著降低LPS诱导的大鼠海马神经元PDE4B蛋白表达水平的升高（P〈0.05）;Western蛋白印迹实验结果表明,FA 50和100 mg·kg-1可逆转LPS对CREB和p-CREB蛋白表达的抑制作用（P〈0.05）。结论 FA对LPS诱导的PC12细胞和大鼠海马神经元细胞损伤有保护作用,FA抗神经炎症的作用可能与抑制PDE4表达、激活c AMP/CREB信号通路相关。

英文摘要：

OBJCTIVE To investigate the protective effect of ferulic acid（FA） on lipopolysaccharide（LPS）-induced damage to PC12 cells and hippocampal neurons in Sprague-Dawley（SD） rats and its potential mechanisms. METHODS 1 in vitro study：PC12 cells were pretreated with FA 2.5-40 μmol · L- 1for 12 h and treated with LPS for another 8 h. CCK- 8 kit was used to test PC12 cell viability. Inflammatory cytokines tumor necrosis factor-α（TNF-α）and interleukin-1β（IL-1β）were detected by ELISA kits. Laser scanning confocal microscopy was performed to measure F-actin expression in the cells. 2 in vivo study：FA 25,50 and 100 mg·kg-1was ip given to Sprague-Dawley（SD）rats once a day for 35 d,and from the 29 th day,ip co-administered with LPS（0.2 mg·kg- 1）for 7 d.Immunohistochemistry method was used to determine protein expression of phophodiestera 4B（PDE4B）in the hippocampus of rats. The protein expression of c AMP response element-binding protein（CREB）and phospho CREB（p-CREB）was determined by Western blotting. RESULTS In the in vitro study,compared with LPS group,cell viability was significantly increased in FA 10,20 and 40 μmol·L-1groups（P〈0.05）,while the production of inflammatory cytokines TNF-α and IL-1β decreased（P〈0.05）.The structure and distribution of cytoskeletal protein F-actin were ameliorated markedly in PC12 cells. In the in vivo study,hematoxylin-eosin（HE）staining showed that pretreatment with FA（50 and 100 mg·kg-1）alleviated the damage to the hippocampus induced by LPS in SD rats. Immunohistochemistry showed that FA（50 and 100 mg·kg-1）pretreatment effectively prevented LPS-induced up-regulation of PDE4 B expression in the hippocampus of rats（P〈0.05）. Western blotting analysis showed that the inhibitory effects on the protein expressions of CREB and p-CREB induced by LPS were altered by FA（50 and100 mg·kg-1）pretreatment（P〈0.05）. CONCLUSION FA can protect against LPS induced damage to PC12 cells and hippocampal neurons of rats