摘要
目的:观察安石榴苷(PUN)对慢性不可预知温和应激(CUMS)模型小鼠行为学和肠道菌群的影响,探究PUN抗抑郁的作用机制。方法:将48只C57BL/6小鼠以9种CUMS方法在28 d内建立小鼠抑郁模型,并将造模成功小鼠随机分为PUN高、中、低剂量用药组(50、25、12.5 mg/kg)和模型组。用药组连续6周灌胃给药,给药结束后通过糖水偏好实验、强迫游泳实验、悬尾实验、旷场实验等检测小鼠抑郁样行为;免疫组化法检测小肠黏膜屏障蛋白ZO-1、Occludin的表达;qPCR法检测肠壁炎症相关因子NOD2、NRLP3、IL-6和TNF-αmRNA的表达;ELISA法检测血清中LPS、IL-6和TNF-α水平及小鼠全脑中5-羟色胺(5-HT)和多巴胺(DA)的水平;16S rDNA检测肠道菌群。结果:与模型组相比,给药组小鼠的体质量和糖水偏好度显著上升,旷场实验的小鼠活动增加,强迫游泳不动时间和悬尾不动时间显著降低(P<0.05),同段小肠黏膜ZO-1、Occludin的表达量增加;血清中LPS、IL-6和TNF-α水平显著降低,脑内5-HT和DA水平显著升高(P<0.01),肠道菌群结构改变显著。结论:PUN可改善CUMS模型小鼠的抑郁症状,其作用机制可能与改善肠道菌群,减轻肠壁炎症和损伤有关。
Objective:To investigate the effect of punicalagin(PUN)on depression-like behaviors and intestinal flora of chronic unpredictable mild stress(CUMS)model mice,and to explore the antidepressant mechanism of PUN.Methods:Forty-eight C57BL/6 mice were used to establish depression models in 28 days by 9 CUMS methods,and the mice were randomly divided into high,medium,low dose groups(50,25 and 12.5 mg/kg)and model group.After administration of 6 weeks,the depression-like behaviors of mice were detected by sugar preference test,forced swimming test,tail suspension test and open field test;the expressions of intestinal mucosal barrier proteins ZO-1 and Occludin were detected by immunohistochemistry assay;the mRNAs of inflammatory related factors NOD2,NRLP3,IL-6 and TNF-αwere detected by qPCR;the LPS,IL-6,TNF-αin serum,and the levels of 5-HT and DA in the whole brain were detected by ELISA;the intestinal flora was detected by16S rDNA.Results:Compared with model group,the body weight and sugar preference of the PUN treated groups increased significantly,the activity in the open field experiment increased obviously,and the immobility time of forced swimming and tail suspension decreased significantly(P<0.05);the expression of mucosal barrier proteins ZO-1 and Occludin increased in the same segment of small intestine;the levels of LPS,IL-6 and TNF-αin serum,the levels of 5-HT and DA in brain were significantly increased(P<0.01);the components of intestinal flora changed significantly.Conclusion:PUN can improve the depressive symptoms of CUMS mice,and the mechanism may be related to optimizing the intestinal flora,alleviating the inflammation and injury of intestinal wall.
作者
许萍
庞振振
黄淑芸
洪宗元
钟树志(指导)
XU Ping;PANG Zhenzhen;HUANG Shuyun;HONG Zongyuan;ZHONG Shuzhi(Wannan Medical College,Wuhu 241002,China)
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2023年第1期65-70,共6页
Chinese Journal of Immunology
基金
国家自然科学基金项目(81973828,81603388)
安徽省高校自然科学重大项目(KJ2020ZD56)
皖南医学院大学生科研基金项目(WK2020S59)。
关键词
安石榴苷
抑郁症
肠道菌群
肠黏膜屏障
Punicalagin
Depression
Intestinal flora
Intestinal mucosal barrie
