摘要
探讨左归降糖解郁方对糖尿病并发抑郁症大鼠肠道菌群和短链脂肪酸的调控以及神经炎症的影响。建立糖尿病并发抑郁症大鼠模型并随机分为4组:模型组、阳性药(二甲双胍+氟西汀)组以及左归降糖解郁方低、高剂量组,另设空白组,每组8只。随后,对大鼠进行抑郁样行为检测;采集脑脊液检测促炎性细胞因子[白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)],采集血清检测下丘脑-垂体-肾上腺轴(HPA轴)相关蛋白[促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)和皮质醇(CORT)]和葡萄糖代谢。收集各组肠道内容物,进行肠道菌群16S rRNA测序分析和短链脂肪酸(SCFAs)测序。结果提示,左归降糖解郁方不仅可以改善糖尿病并发抑郁症大鼠糖代谢(P<0.01),缓解抑郁样行为(P<0.05)和HPA轴亢进(P<0.05或P<0.01),还可以改善脑内炎症反应,表现为脑脊液中促炎性细胞因子显著降低(P<0.05或P<0.01);并改善肠道菌群,使糖尿病并发抑郁症大鼠肠道菌群趋于空白组发展,表现为提高糖尿病并发抑郁症大鼠肠道菌群中厚壁菌门Firmicutes的丰度;并能够显著提高SCFAs(乙酸、丁酸、戊酸和异戊酸)的含量(P<0.01)。因此推测,左归降糖解郁方可有效改善肠道菌群紊乱,并调控SCFAs,从而改善糖尿病并发抑郁症糖代谢紊乱和抑郁样行为。
This study aimed to investigate the regulatory effects of Zuogui Jiangtang Jieyu Formula(ZJJ) on the intestinal flora, short chain fatty acids(SCFAs), and neuroinflammation in rats with diabetes mellitus complicated depression(DD). The DD model was established in rats and model rats were randomly divided into a model group, a positive drug(metformin + fluoxetine) group, a ZJJ low-dose group, and a ZJJ high-dose group, with eight rats in each group. Another eight rats were assigned to the blank group. Subsequently, depressive-like behavior test was conducted on the rats, and cerebrospinal fluid samples were collected to measure pro-inflammatory cytokines [interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α)]. Blood serum samples were collected to measure proteins related to the hypothalamic-pituitary-adrenal axis(HPA axis), including corticotropin-releasing hormone(CRH), adrenocorticotropic hormone(ACTH), and cortisol(CORT), as well as glucose metabolism. Gut contents were collected from each group for 16S rRNA sequencing analysis of intestinal flora and SCFAs sequencing. The results indicated that ZJJ not only improved glucose metabolism in DD rats(P<0.01) but also alleviated depressive-like behavior(P<0.05) and HPA axis hyperactivity(P<0.05 or P<0.01). Besides, it also improved the neuroinflammatory response in the brain, as evidenced by a significant reduction in pro-inflammatory cytokines in cerebrospinal fluid(P<0.05 or P<0.01). Additionally, ZJJ improved the intestinal flora, causing the intestinal flora in DD rats to resemble that of the blank group, characterized by an increased Firmicutes abundance. ZJJ significantly increased the levels of SCFAs(acetic acid, butyric acid, valeric acid, and isovaleric acid)(P<0.01). Therefore, it is deduced that ZJJ can effectively ameliorate intestinal flora dysbiosis, regulate SCFAs, and thereby improve both glucose metabolism disturbances and depressive-like behavior in DD.
作者
李薇
雷诗卉
王瑾茜
刘林
杨蕙
LI Wei;LEI Shi-hui;WANG Jin-xi;LIU Lin;YANG Hui(Medical Innovation Experimental Center,the First Hospital of Hunan University of Chinese Medicine,Changsha 410000,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2024年第1期208-215,共8页
China Journal of Chinese Materia Medica
基金
湖南省中医药管理局科研计划项目(D2022099)
湖南省自然科学基金项目(2023JJ30476,2021JJ30018)
湖南省科技创新人才计划项目(2021RC3102)。
关键词
糖尿病
抑郁症
左归降糖解郁方
肠道菌群
短链脂肪酸
diabetes mellitus
depression
Zuogui Jiangtang Jieyu Formula
gut microbiota
short chain fatty acids
