摘要 目的探讨远志提取物对抑郁大鼠肠道菌群的影响及其可能的作用机制。方法采用孤养结合慢性不可预知性温和应激(chronic unpredictable mild stress,CUMS)方法建立抑郁大鼠模型,SD大鼠随机分为对照组、空白给药组、模型组、氟西汀(2mg/kg)组和远志提取物高、中、低剂量(1.5、1.0、0.5g/kg)组。观察各组大鼠行为学并检测海马组织单胺类神经递质及其代谢物水平;采用ELISA法检测大鼠血清中促肾上腺皮质激素释放因子(corticotropin-releasing factor,CRF)、促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)、皮质酮(corticosterone,CORT)、白细胞介素-6(interleukin-6,IL-6)和脂多糖(lipopolysaccharide,LPS)水平;采用透射电镜(TEM)观察大鼠十二指肠和结肠上皮的超微结构变化;采用16S rRNA测序检测大鼠粪便肠道菌群的结构变化。结果与模型组比较,远志提取物可明显改善大鼠的抑郁样行为(P<0.05、0.01、0.001),显著升高海马组织中去甲肾上腺素(norepinephrine,NE)、5-羟色胺(5-hydroxytryptamine,5-HT)、二羟基苯乙酸(dihydroxyphenyl acetic acid,DOPAC)和5-羟吲哚乙酸(5-hydroxyindoleacetic acid,5-HIAA)水平(P<0.05、0.01、0.001),显著降低血清中CRF、ACTH、CORT、IL-6和LPS水平(P<0.01、0.001),减轻其下丘脑-垂体-肾上腺皮质(hypothalamic-pituitary-adrenal,HPA)轴的功能亢进状态;同时远志提取物对大鼠肠道内的菌群失调具有调节作用。结论远志提取物可以通过改善肠道菌群结构、恢复肠屏障功能、降低肠源性内毒素释放、减轻机体炎症水平,从而发挥抗抑郁作用。 Objective To explore the effect and mechanism of Yuanzhi(Polygalae Radix) extract on gut microbiota of depressed rats. Methods Orphans and chronic unpredictable mild stress(CUMS) were used to establish depression rats model. SD rats were randomly divided into control group, control administration group, model group, fluoxetine(2 mg/kg) group and extract of Polygalae Radix high-, medium-and low-dose(1.5, 1.0, 0.5 g/kg) groups. Behavior of rats in each group were observed and levels of monoamine neurotransmitters and their metabolites in hippocampus were detected;ELISA were used to detect levels of corticotropin-releasing factor(CRF), adrenocorticotropic hormone(ACTH), corticosterone(CORT), interleukin-6(IL-6) and lipopolysaccharide(LPS) in serum of rats;Transmission electron microscopy(TEM) was used to observe ultrastructural changes of duodenum and colon epithelium of rats;16 S rRNA sequencing was used to detect structural changes of gut microbiota in feces of rats. Results Compared with model group, depression-like behaviors of rats in Polygalae Radix extract groups were significantly improved(P < 0.05, 0.01, 0.001);Levels of norepinephrine(NE) and 5-hydroxytryptamine(5-HT), dihydroxyphenyl acetic acid(DOPAC) and 5-hydroxyindoleacetic acid(5-HIAA) in hippocampus were significantly increased(P < 0.05, 0.01, 0.001);Levels of CRF, ACTH, CORT, IL-6 and LPS in serum were significantly reduced(P < 0.01, 0.001), hyperfunction of hypothalamic-pituitary-adrenal(HPA) axis was alleviated;Polygalae Radix extract had a regulatory effect on imbalance of gut microbiota flora in rats. Conclusion Polygalae Radix extract plays an antidepressant effect by improving structure of gut microbiota, restoring intestinal barrier function, reducing release of intestinal endotoxin and inhibiting inflammation.
机构地区 首都医科大学中医药学院
出处 《中草药》 CAS CSCD 北大核心 2021年第8期2313-2323,共11页 Chinese Traditional and Herbal Drugs
基金 国家自然科学基金青年基金项目(81703670)。
关键词 远志提取物 抑郁症 慢性不可预知性温和应激 肠道菌群 16S rRNA Polygalae Radix extract depression chronic unpredictable mild stress gut microbiota 16S rRNA
