毛蕊花糖苷对抑郁症大鼠行为学和前额叶皮层内质网应激的影响

Effect of acteoside on behavioral changes and endoplasmic reticulum stress in prefrontal cortex of depressive rats

目的:观察毛蕊花糖苷(acteoside)对抑郁症大鼠行为学及前额叶皮层内质网应激(endoplasmic reticulum stress,ERS)的影响,探讨毛蕊花糖苷的抗抑郁机制。方法:将108只健康雄性SD大鼠按照随机数字表法分为对照组、模型组、阳性对照氟西汀(20 mg/kg)组和毛蕊花糖苷低、中、高剂量(30 mg/kg、60 mg/kg、120 mg/kg)组,每组18只。采用慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)结合孤养的方式制备大鼠抑郁模型。氟西汀组和毛蕊花糖苷各剂量组分别按剂量连续灌胃给药3周,对照组和模型组每日以等体积生理盐水灌胃。采用旷场实验和糖水偏好实验观察大鼠抑郁样行为变化;免疫荧光组化法检测大鼠前额叶皮层ERS通路的关键因子葡萄糖调节蛋白78(glucose-regulated protein 78,GRP78)和C/EBP同源蛋白(C/EBP homologous protein,CHOP)的表达情况;分光光度计检测大鼠前额叶皮层caspase-3的活性。结果:与对照组比较,模型组、氟西汀组及毛蕊花糖苷各剂量组大鼠旷场实验总行程、中间停留时间及糖水摄取量均下降,前额叶皮层GRP78和CHOP的表达均明显增加,caspase-3酶活性明显升高(P<0.05);与模型组比较,氟西汀组和毛蕊花糖苷各剂量组旷场实验总行程、中间停留时间及糖水摄取量均增加,GRP78和CHOP的表达均明显降低,caspase-3酶活性明显下降(P<0.05)。结论:毛蕊花糖苷可以改善抑郁症大鼠的抑郁样行为,其机制可能与其抑制前额叶皮层ERS通路并减少神经元凋亡有关。

AIM:To explore the effect of acteoside on behavioral changes and endoplasmic reticulum stress(ERS)in prefrontal cortex of depressive rats.METHODS:Sprague-Dawley(SD)rats(n=108)were randomly divided into6groups:control group,model group,fluoxetine(20mg/kg)group,low-dose(30mg/kg)acteoside group,medium-dose(60mg/kg)acteoside group and high-dose(120mg/kg)acteoside group,with18rats in each group.The depressive-like rat model was established by chronic unpredictable mild stress(CUMS)combined with solitary way for28d.The rats in fluoxetine group and acteoside groups were treated with fluoxetine(20mg/kg)or acteoside(30mg/kg,60mg/kg and120mg/kg)once daily by intragastric administration for3weeks.The rats in control group and model group were both given equal volume of saline by intragastric administration for3weeks.The behavioral changes were detected by the open-field test and sugar preference experiment.The protein expression of glucose-regulated protein78(GRP78)and C/EBP homologous protein(CHOP)was assessed by immunofluorescence and Western blot.The caspase-3activity was measured by spectrophotometer.RESULTS:Compared with control group,the total distance,time spent in the center and sugar intake were all decreased,the expression of GRP78and CHOP was increased,and the activity of caspase-3was increased in model group,fluoxetine group and acteoside groups(P<0.05).Compared with model group,the total distance,time spent in the center and sugar intake were increased,the expression of GRP78and CHOP was reduced,and the activity of caspase-3was decreased(P<0.05)in fluoxetine group and acteoside groups.CONCLUSION:Acteoside improves depressive-like behaviors in depressive rats,which may be related to the inhibition of ERS and neuronal apoptosis in prefrontal cortex.