慢性不可预见刺激诱导大鼠抑郁行为与上调GSK-3β表达及氧化/抗氧化应激失衡密切相关

Depressive behaviors of rats induced by unpredictable stress involved in up-regulation of GSK-3β expression and imbalance of oxidative and anti-oxidative system in rat brain

目的:研究慢性不可预见刺激诱导大鼠抑郁行为与糖原合成激酶-3β(glycogen synthase kinase-3β,GSK-3β)的表达及氧化应激损伤之间的关系。方法:采用慢性不可预见刺激(chronically unpredicted stress,CUS)诱导大鼠建立抑郁症模型。30只Sprague Dawley(SD)大鼠随机分为对照组和模型组各15只,以旷场实验和被动游泳实验评价大鼠焦虑、绝望样抑郁行为;以大鼠海马过氧化氢酶(catalase,CAT)、超氧化物歧化酶(superoxide dismutase,SOD)活力及丙二醛(malondialdehyde,MDA)含量评价海马氧化应激和抗氧化应激水平;以q RT-PCR和Western blot分别检测并评价海马GSK-3βm RNA及蛋白表达变化。结果:与对照组相比,模型组旷场实验水平运动和垂直运动明显减少(P=0.000)、被动游泳实验不动时间明显延长(P=0.000)、CAT及SOD活力明显降低(P=0.000)、MDA含量明显升高(P=0.014)、GSK-3βm RNA和蛋白表达明显增加(P=0.000;P=0.028)。结论:CUS诱导大鼠出现明显焦虑、绝望样抑郁行为,其机制可能与上调GSK-3β表达及氧化应激系统功能失衡有关。

Objective：To investigate the relationship between the depressive behaviors of rats induced by chronically unpredictable stress（CUS） and the change of glycogen synthase kinase-3beta（GSK-3β） expression and oxidative stress. Methods：Totally 30 Sprague Dawley（SD）rats were randomly divided into control group and model group. CUS with solitary condition was taken to establish rat depression model. The open-field test（OFT）and forced swim test（FST）were used to assess the anxiety- and despair-like depression behaviors of rats;superoxide dismutase（SOD）,catalase（CAT）,and malondialdehyde（MDA） levels were used to evaluate oxidative stress and anti-oxidative stress level;the real time PCR and Western blot were used to determine and assess the change of GSK-3β m RNA and protein expression in rat＇s brains. Results：It showed that the movements in OFT decreased（P=0.000）and the immobility time in FST increased significantly（P=0.000）;CAT and SOD activities decreased significantly（P=0.000）with obviously increased MDA level（P=0.014）and GSK-3β m RNA and protein expression（P=0.000;P=0.028）in model group compared with those in control group. Conclusion：The mechanism of the anxiety- and despair-like depression behaviors of rats induced by CUS maybe involved in upregulating GSK-3β expression and oxidative stress.