宁神灵颗粒对抑郁模型大鼠海马神经元凋亡、自噬及氧化应激损伤的影响

Effect of ningshenling granule on apoptosis, autophagy and oxidative stress injury of hippocampal neurons in depression model rats

目的研究宁神灵颗粒对抑郁模型大鼠海马神经元凋亡、自噬及氧化应激损伤的影响。方法清洁级雄性SD大鼠随机分为对照组、模型组、宁神灵组、氟西汀组,后3组给予慢性不可预知性温和刺激建立抑郁模型,连续56 d,后28 d模型组给予生理盐水灌胃、宁神灵组给予宁神灵颗粒灌胃、氟西汀组给予氟西汀灌胃。采用行为学实验评价抑郁程度,检测海马中凋亡及自噬表达量、氧化应激指标含量。结果与对照组比较,模型组糖水偏爱度明显降低,强迫游泳的不动时间明显延长,海马中Caspase-3、Bax、LC3-Ⅱ/LC3-I、Beclin-1的表达及ROS、MDA的含量明显增加,Bcl-xL、P62的表达及SOD、GSH的含量明显减少;与模型组比较,宁神灵组及氟西汀组大鼠的糖水偏爱度明显增加,强迫游泳的不动时间明显缩短,海马中Caspase-3、Bax、LC3-Ⅱ/LC3-I、Beclin-1的表达及ROS、MDA的含量明显减少,Bcl-xL、P62的表达及SOD、GSH的含量明显增多。结论宁神灵颗粒能够改善抑郁模型大鼠的抑郁情绪,其机制可能与调节海马中凋亡、自噬及氧化应激有关。

Objective To study the effects of Ningshenling Granule on apoptosis,autophagy and oxidative stress injury of hippocampal neurons in depression model rats.MethodsClean male SD rats were randomly divided into the control group,model group,ningshenling group and fluoxetine group.The latter three groups were given chronic unpredictable mild stimulation to establish depression model for 56 d.During the latter 28 d,the model group was given gastric perfusion of normal saline,the ningshenling group was given gastric perfusion of ningshenlinggranule,and the fluoxetine group was given gastric perfusion of fluoxetine.The degree of depression was evaluated by behavioral experiment,and the expression of apoptosis,autophagy genes and the contents of oxidative stress indexes in hippocampus were detected.ResultsCompared with the control group,the sugar preference of the model group was significantly decreased,the immobility time of forced swimming was significantly prolonged,the expression of Caspase-3,Bax,LC3-Ⅱ/LC3-I,Beclin-1 in hippocampus and the contents of ROS and MDA were significantly increased,while the expression of Bcl-xL,P62 and the contents of SOD and GSH were significantly decreased.Compared with the model group,the sugar preference of ningshenling group and fluoxetine group were significantly increased,the immobility time of forced swimming was significantly shortened,the expression of Caspase-3,Bax,LC3-Ⅱ/LC3-I,Beclin-1 and the contents of ROS and MDA in hippocampus were significantly decreased,while the expression of Bcl-xL,P62 and the contents of SOD and GSH were significantly increased.ConclusionNingshenling Granule can improve the depressive mood of depression model rats,and its mechanism may be related to the regulation of apoptosis,autophagy and oxidative stress in hippocampus.