西南医科大学学报2024，Vol.47Issue(2)：166-171,6.DOI:10.3969/j.issn.2096-3351.2024.02.014
枸橼酸坦度螺酮组合物通过抑制神经元氧化损伤和调节小胶质细胞活化发挥抗抑郁作用
Tandospirone citrate composition exerts antidepressant effects by inhibiting neuronal oxidative damage and microglial activation
摘要
Abstract
Objective Different tandospirone citrate compositions(TCCs)were screened to assess their effectiveness in improv-ing depressive behaviors in mice and to explore the neuroprotective effects of the most effective combinations.Methods Animal behav-ioral experiments and in vitro cellular experiments were used.In animal experiments,the effects of five TCCs on depression-like behav-iors in mice were evaluated by the forced swim test(FST)and tail suspension test(TST).In vitro experiments were conducted to inves-tigate the effects of TCC-4,which exhibited the best performance,on inhibiting hydrogen peroxide(H2O2)-induced damage in PC-12 cells and lipopolysaccharide(LPS)-induced neuroinflammation in BV-2 cells.Results In FST and TST experiments,TCCs signifi-cantly reduced the resting time of mice(P<0.05),showing their antidepressant-like effects.In H2O2-induced PC-12 cells,the best-performing TCC-4 was found to effectively inhibit cell death,reactive oxygen species(ROS)production,and mitochondrial membrane potential(MMP)reduction(P<0.001).Additionally,TCC-4 could attenuate LPS-induced BV-2 cell activation and phagocytosis(P<0.001).Conclusion TCCs,especially TCC-4,showed favorable antidepressant effects.The mechanism of action might be related to the inhibition of oxidative damage in neurons and the regulation of microglia activation.These findings provided support for the poten-tial of TCC-4 as a novel antidepressant drug and laid the foundation for further studies on its clinical application.关键词
抑郁症/枸橼酸坦度螺酮组合物/氧化应激/神经炎症/小胶质细胞Key words
Depression/Tandospirone citrate compositions/Oxidative stress/Neuroinflammation/Microglia分类
医药卫生引用本文复制引用
邓岚,曾娟,王征琴,唐新新,陈刚,吴建明,吴安国..枸橼酸坦度螺酮组合物通过抑制神经元氧化损伤和调节小胶质细胞活化发挥抗抑郁作用[J].西南医科大学学报,2024,47(2):166-171,6.基金项目
国家自然科学基金青年项目(81903829) （81903829）
