针刺对慢性应激抑郁大鼠海马AMPK/ULK1信号通路和自噬的影响OA北大核心CSTPCDMEDLINE

Objective To observe the effect of manual acupuncture stimulation on changes of behavior and hippocampal signaling pathways of AMP-activated kinase(AMPK)/UNC-51-like kinase 1(ULK1)in rats with chronic unpredictable mild stress(CUMS)-induced depression,so as to explore its molecular mechanism underlying improvement of depression.Methods Thirty-two male SD rats were randomly divided into normal control,model,acupuncture and medication(fluoxetine)groups,with 8 rats in each group.The depression model was established by using CUMS(fasting,water depredation,restraint,swimming in cold water,crowding,stroboscope stimulation,and tail clipping,each of which was used once a week)for 6 weeks.Manual acupuncture stimulation was applied to"Baihui"(GV20)and"Yintang"(EX-HN3)for 10 min,once daily,6 times a week for 6 weeks before every-day modeling.Rats of the medication group received gavage of fluoxetine(10 mg/kg)once a day for 6 weeks before every-day modeling.The percentage of sucrose preference,and the percentages of open arm times and open arm time in the elevated plus maze experiments were detected.The expression levels of AMPK,phosphorylated(p)-AMPK,ULK1,p-ULK1,mammalian target of rapamycin(mTOR)and p-mTOR proteins in the hippocampus tissue were detected by Western blot,and the expression of autophagy effecting protein(Beclin-1)and the selective autophagy receptors(p62)mRNA in the hippocampal tissue was detected using real-time fluorescence quantitative PCR,respectively.Results Compared with the normal group,the percentage of sucrose preference,percentage of times of entering the open arm and percentage of open arm time,the expression levels of p-AMPK/AMPK ratio,p-ULK1/ULK1 ratio of proteins,and Beclin-1 mRNA were significantly decreased(P<0.01,P<0.05),and the expression levels of p-mTOR/mTOR ratio and p62 mRNA were significantly increased(P<0.01,P<0.05)in the model group.In comparison with the model group,the percentage of sucrose preference,percentage of open arm times and open arm time,the expression levels of p-AMPK/AMPK ratio,p-ULK1/ULK1 ratio of proteins,and Beclin-1 mRNA were significantly increased in both acupuncture and medication groups(P<0.01,P<0.05),while the expression levels of p-mTOR/mTOR ratio of proteins,and p62 mRNA were markedly decreased only in the medication group(P<0.05).Conclusion Acupuncture treatment can alleviate depression-like behavior in CUMS rats,which may be related to its functions in up-regulating AMPK/ULK1 signaling pathway to induce cellular autophagy in the hippocampus.