菊淀粉型巴戟天寡糖对慢性应激模型小鼠抑郁、焦虑样行为的改善及对调节性T细胞数量的调节作用

Inulin-type oligosaccharides of Morinda officinalis regulate number of regulatory T cells in chronic unpredictable stress model mice while improving their depression and anxiety-like behavior

目的评价抗抑郁药菊淀粉型巴戟天寡糖(IOMO)对慢性不可预知应激(CUS)模型小鼠抑郁、焦虑样行为的影响,并探究其对CUS模型小鼠小肠上皮和脾组织中调节性T细胞(Tr细胞)的调节作用。方法连续28 d给予小鼠CUS建立抑郁模型。实验分为正常对照组、CUS模型组、CUS+氟西汀(FLX)组和CUS+IOMO组。于应激首日开始每天1次ig给予IOMO 50 mg·kg^(-1)或FLX 10 mg·kg^(-1),连续给药28 d。在CUS造模前和结束时,采用蔗糖偏嗜实验(SPT)各检测1次小鼠蔗糖偏嗜度。CUS造模后,以开场实验(OFT)评价焦虑样行为;以强迫游泳实验(FST)和新奇抑制摄食实验(NSF)评价抑郁样行为;采用流式细胞术检测小鼠小肠上皮和脾组织中Tr细胞数量。结果慢性应激28 d后,与正常对照组相比,CUS模型组小鼠在SPT中蔗糖偏嗜度显著降低(P<0.01);在OFT中进入中央区的累计次数和累计停留时间显著减少(P<0.05),表现出焦虑样行为;在FST中不动时间显著延长(P<0.05),在NSF中摄食潜伏期显著延长(P<0.01),表现出抑郁样行为;小鼠小肠上皮和脾组织中Tr细胞数量显著减少(P<0.05)。与CUS模型组相比,CUS+IOMO组和CUS+FLX组小鼠抑郁样和焦虑样行为显著缓解,小肠上皮和脾组织中Tr细胞数量显著增加(P<0.05)。相关性分析显示,小肠上皮和脾组织中Tr细胞数目变化与蔗糖偏嗜度变化之间具有显著相关性(Pearson相关系数r分别为0.5044和0.7267,P<0.05)。结论在CUS模型小鼠上,IOMO在表现出抗抑郁、抗焦虑作用的同时可增加小肠上皮和脾组织中Tr细胞的数目,这可能是其抗抑郁作用机制之一。

OBJECTIVE To assess the effects of antidepressant inulin-type oligosaccharides of Morinda officinalis(IOMO)on depressive and anxiety-like behaviors in chronically stress model mice,investigate the effects of IOMO on regulatory T cells(Tr cells)in the intestinal epithelium and spleen of chronically-stressed model mice,and to offer new clues to the antidepressant mechanism of oligosaccharide components.METHODS A chronic unpredictable stress(CUS)depression model was established.The mice were divided into the normal control group,CUS model group,CUS+fluoxetine(FLX)group and CUS+IOMO group.IOMO 50 mg·kg^(-1)or FLX 10 mg·kg^(-1)was ig given to the mice from the first day of modeling for 28 consecutive days.The sucrose preference test(SPT)of mice was conducted to evaluate the sucrose preference of mice at the beginning and end of modeling.The opening filed test(OFT)was used to investigate the anxiety-like behavior.The forced swimming test(FST)and novel inhibition feeding test(NSF)were used to study the depression-like behavior.Flow cytometry was used to observe the changes of Tr cells in intestinal epithelial lymphocytes and spleens of mice in each group.RESULTS After 28 days of CUS,the preference for sugar water in the CUS model group was significantly reduced in the SPT compared with the control group(P<0.01),so were the latency to enter the central area(P<0.05)and the total number of times of entry(P<0.05)in the OFT.Compared with the control group,the immobility time of mice was significantly prolonged(P<0.05)in the FST,so was the first feeding latency(P<0.01)in the NSF.Administration of IOMO or FLX could significantly reverse the above changes(P<0.05).The results of flow cytometry showed that the number of Tr cells in the intestinal epithelium and spleen of the CUS model group decreased significantly(P<0.05)compared with the control group.Compared with CUS model group,the number of Tr cells in the intestinal epithelium and spleen of mice in the CUS+IOMO group and CUS+FLX group was significantly increased(P<0.05).At the same time,correlation analysis showed that there was a significant correlation between the number of Tr cells in the intestinal epithelium and spleen and the changes in sucrose preference(P<0.05).CONCLUSION IOMO has significant anti-anxiety and anti-depression effects in CUS model mice,and can increase the number of Tr cells in the intestinal epithelium and spleen,which may be one of its important mechanisms.