尾静脉注射AMPKα1高表达腺病毒对抑郁症模型大鼠线粒体损伤和代谢的调节作用

Regulation of intravenous injection of adenovirus with high expression of AMPKα1 on mitochondrial damage and metabolism in chronic stress depression model rats

目的:探究尾静脉注射腺苷酸活化蛋白激酶α1(AMPKα1)高表达腺病毒对抑郁症模型大鼠线粒体损伤和代谢的调节作用。方法:采用不可预见温和应激法建立大鼠抑郁症模型,尾静脉注射AMPKα1高表达腺病毒。Morris水迷宫实验评价大鼠记忆力,旷场实验评价大鼠自主探究行为,HE染色观察大鼠海马和前额叶皮质区病理改变情况,Western blot检测AMPKα1、Bcl-2、Bax、Caspase-3、Caspase-9、PGC-1α和GLUT4蛋白表达,试剂盒检测SOD、MDA和LDH含量,RT-PCR检测AMPKα1、PGC-1α和GLUT4 mRNA表达。结果:与CUMS+Ad-NC组相比,CUMS+Ad-AMPKα1组大鼠AMPKα1 mRNA和蛋白表达显著上调,逃避潜伏期时间显著缩短,目标象限记忆时间显著延长,水平活动次数和垂直站立次数显著增加,脑损伤显著减轻,Bcl-2蛋白表达显著上调,Bax、Caspase-3和Caspase-9蛋白表达显著下调,SOD含量显著增多,LDH和MDA含量显著减少,PGC-1α和GLUT4表达显著上调。结论:尾静脉注射AMPKα1高表达腺病毒可改善抑郁症模型大鼠学习记忆能力、自主探究行为和糖代谢,缓解脑损伤、线粒体损伤和氧化应激,从而缓解抑郁症。

Objective:To investigate regulation effects of adenovirus with high expression of AMPKα1 by intraven ovs injection on mitochondrial damage and metabolism in chronic stress depression model rats.Methods:Depression model was established by unpredictable mild stress and intravenous injection of adenovirus with high expression of AMPKα1.Memory of rats was evaluated by Morris water maze test.Self-exploration behavior of rats was evaluated by open field experiment.Pathological changes of hippocampus and prefrontal cortex were observed by HE staining.Protein expressions of AMPKα1,Bcl-2,Bax,Caspase-3,Caspase-9,PGC-1αand GLUT4 were detected by Western blot.Contents of SOD,MDA and LDH were detected by kit.mRNA expressions of AMPKα1,PGC-1αand GLUT4 were detected by RT-PCR.Results:Compared with CUMS+Ad-NC group,mRNA and protein expressions of AMPKα1 were significantly up-regulated,time to escape latency was significantly reduced,target quadrant memory time was significantly increased,number of horizontal activities and vertical standing times were significantly increased,brain damage was significantly reduced,expression of Bcl-2 protein was significantly up-regulated,expressions of Bax,Caspase-3 and Caspase-9 proteins were significantly down-regulated,content of SOD was significantly increased,contents of LDH and MDA were significantly decreased,expressions of PGC-1αand GLUT4 were significantly up-regulated in CUMS+Ad-AMPKα1 group.Conclusion:Intravenous injection of adenovirus with high expression of AMPKα1 can relieve depression in depression model rats by improving learning and memory ability,self-exploration behavior and glucose metabolism in depression model rats,alleviating brain damage,mitochondrial damage and oxidative stress.