浙江中医药大学学报2025，Vol.49Issue(12)：1526-1535,10.DOI:10.16466/j.issn1005-5509.2025.12.004
基于"脑-肠轴"研究围绝经期抑郁症大鼠的肠道微生物变化
Study on Intestinal Microbial Changes in Perimenopausal Depression Rats Based on Brain Gut Axis
摘要
Abstract
[Objective]To compare the differences of neuroendocrine and intestinal microflora among normal,perimenopausal,depression and perimenopausal depression rats,and to explore the potential mechanism of"brain-gut axis"in perimenopausal depression.[Methods]Perimenopausal model was established by using bilateral ovariectomy(OVX),and depression model was induced by chronic unpredictable mild stress(CUMS).Forty female SD rats with regular estrus were divided into sham surgery(Sham)group,perimenopausal period model(OVX)group,depression model(CUMS)group and perimenopausal period combined with depression model(OVX+CUMS)group,with 10 rats in each group,using the above two modeling methods separately or in combination.After modeling,serum levels of estradiol,testosterone,and progesterone were measured,and sucrose preference,tail suspension and open field experiments were performed to evaluate depressive behavior.Hematoxylin-eosin(HE)staining was used to observe the changes in uterine tissue.Changes of intestinal microflora in different models were investigated through 16S rDNA amplicon sequencing technology.The levels of norepinephrine(NE),dopamine(DA),and 5-hydroxytryptamine(5-HT)in brain homogenate were determined by enzyme-linked immunosorbent assay(ELISA).The levels of nitric oxide(NO),lipid peroxide(LPO),malondialdehyde(MDA),activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in peripheral blood serum were also measured.[Results]Compared with Sham group,the levels of estradiol and testosterone in OVX group were significantly reduced(P<0.05),the testosterone level in CUMS group was significantly reduced(P<0.05),and the levels of estradiol and progesterone in OVX+CUMS group were significantly reduced(P<0.05).Compared with CUMS group,the levels of estradiol and progesterone in OVX+CUMS group were significantly reduced(P<0.05).In terms of behavior,compared with Sham group,CUMS group(P<0.01)and OVX+CUMS group(P<0.05)showed a significant decrease in sugar water preference.The number of open field standing times(P<0.01)time to enter the central area(P<0.05)and total distance of movement(P<0.05)were significantly reduced in both groups,and the time for tail suspension or reduced movement was significantly increased(P<0.01).Compared with OVX group,OVX+CUMS group showed a significant decrease in sugar water preference(P<0.01),as well as a significant reduction in the number of open field stands(P<0.01)and the time to enter the central area(P<0.01).HE staining showed that estrogen deficiency caused cervical atrophy,and the endometrial thickness(P<0.01)and muscle layer thickness(P<0.01)of OVX group and OVX+CUMS group were significantly reduced.CUMS group also had mild pathological changes(P<0.05).In terms of gut microbiota,the richness and evenness(alpha diversity)of each group were significantly reduced compared with Sham group(P<0.05,P<0.01),and the differences(beta diversity)between microbiota were also different.In terms of species composition,CUMS modeling led to a significant reduction in the dominant species of normal gut microbiota.The microbiota structure of OVX+CUMS group was similar to that of CUMS group,but there were specific changes.The biochemical results showed that compared with Sham group,NE level decreased(P<0.01)and DA increased(P<0.01)in OVX group,while NE,DA and 5-HT levels decreased(P<0.01,P<0.05)in CUMS group and CUMS+OVX group;the levels of GSH-Px and NO in OVX group decreased(P<0.01,P<0.05),while the levels of MDA and NO increased(P<0.01)and the activities of SOD and GSH-Px decreased(P<0.01)in CUMS+OVX group,indicating a decrease in the bodys'antioxidant capacity and a higher level of lipid peroxidation.[Conclusion]Depression may affect uterine tissue and hormone secretion through the"brain-gonadal axis",and cause changes in gut microbiota through the"brain-gut axis",which may be related to changes in neurotransmitters and antioxidant capacity.关键词
围绝经期/抑郁/CUMS模型/脑肠轴/脑性腺轴/神经递质/肠道微生物测序/脂质过氧化Key words
perimenopause/depression/CUMS model/brain-gut axis/brain-gonadal axis/neurotransmitters/intestinal microbiota sequencing/lipid peroxidation分类
医药卫生引用本文复制引用
凌云,吕涛,褚燕青,朱科燕,方明笋,戎亦骊..基于"脑-肠轴"研究围绝经期抑郁症大鼠的肠道微生物变化[J].浙江中医药大学学报,2025,49(12):1526-1535,10.基金项目
浙江省医药卫生科技项目(2021KY220) Zhejiang Medical Health Science and Technology Project(2021KY220) （2021KY220）
