氟西汀通过上调海马内溴结构域蛋白4的表达改善慢性束缚应激所致小鼠的抑郁样行为

目的 探讨氟西汀（FLX）对慢性束缚应激（CRS）所致小鼠抑郁样行为及海马内溴结构域蛋白4（BRD4）表达的影响。 方法 24只雄性昆明小鼠随机分为生理盐水对照（NS）组、抑郁模型（CRS）组、氟西汀干预（CRS+FLX）组。慢性束缚应激3周建立小鼠抑郁模型，应激的第8天至第21天 CRS+FLX组于应激前30 min腹腔注射氟西汀（10mg/kg），NS组及CRS组注射等体积生理盐水。采用糖水偏好实验、喷糖实验、强迫游泳实验、新旧事物识别实验和旷场实验检测各组小鼠行为变化；采用Western blotting及Real-time PCR法检测小鼠海马BRD4蛋白和mRNA的表达情况。 结果 与NS组相比，CRS组小鼠表现出明显的抑郁样行为，包括糖水偏好百分比显著降低（P<0.01），喷糖实验舔糖时间缩短（P<0.05），强迫游泳不动时间增加（P<0.01），新事物辨别指数降低（P<0.0001），抗抑郁药FLX干预可逆转CRS所诱导的上述抑郁样行为表现（P<0.05）；与NS组相比，CRS组小鼠海马BRD4蛋白及mRNA的表达明显下调（1.;0000 ± 0.04577 比 0.08337 ± 0.01658；1.0000 ± 0.04379 比 0.6672 ± 0.03193，P<0.05），而FLX可上调抑郁小鼠海马BRD4蛋白及mRNA的表达（0.08337 ± 0.01658 比 0.4983 ± 0.08574；0.6672 ± 0.03193比0.8572 ± 0.03181，P<0.05）。 结论 氟西汀可能通过上调海马BRD4的表达改善小鼠抑郁样行为。

Fluoxetine improving the depression-like behavior induced by chronic restraint stress by up-regulation the expression of bromodomain-containing protein 4 in hippocampus of mouse

Objective To investigate the effect of fluoxetine (FLX) on the expression of bromodomain-containing protein 4 (BRD4) in the hippocampus induced by chronic restraint stress (CRS), with the depression-like behaviour also being determined. Methods Twenty-four male Kunming mice were randomly divided into normal saline(NS) group, CRS group and fluoxetine(FLX) intervention(CRS+FLX) group. The mice of the CRS group were subjected to 3 weeks chronic restraint stress. The mice of CRS+FLX group were treated with fluoxetine by intraperitoneal injection 30 minutes before restraint stress from the 8 to 21 days. The mice in the NS group and CRS group were treated with NS. Depression-like behavior was determined by sucrose preference test, sucrose splash test, forced swimming test, novelty object recognition test and open field test. Expression of BRD4 in the hippocampus was determined by Western blotting and Real-time PCR. Results Compared with NS group, mice in the CRS group showed reduced sucrose preference (P<0.01) and decrease the time spent licking in Sucrose splash test (P<0.05) , increase immobility time in the forced swimming test (P<0.01) and decrease on the discrimination ratio in the novelty object recognition test, while FLX treatment effectively reversed the depression-like behavior induced by CRS (P<0.05) Compared with the NS group, CRS led to significantly decreased expression of BRD4 protein and mRNA in the hippocampus (1.000 ± 0.04577 vs 0.08337 ± 0.01658; 1.000 ± 0.04379 vs 0.6672 ± 0.03193, P<0.05), which was attenuated by FLX treatment (0.08337 ± 0.01658 vs 0.4983 ± 0.08574; 0.6672 ± 0.03193 vs 0.8572 ± 0.03181, P<0.05). Conclusion Our finding indicates that FLX could alleviate CRS-induced depression-like behavior in mice, which might be attributed to the increased expression of BRD4 in the hippocampus.