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.
Zhongguo Zhong Yao Za Zhi. 2024 Jan;49(1):208-215. doi: 10.19540/j.cnki.cjcmm.20230908.401.
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.
本研究旨在探讨左归降糖解郁方（ZJJ）对糖尿病合并抑郁症（DD）大鼠肠道菌群、短链脂肪酸（SCFAs）及神经炎症的调节作用。在大鼠中建立DD模型，将模型大鼠随机分为模型组、阳性药物（二甲双胍+氟西汀）组、ZJJ低剂量组和ZJJ高剂量组，每组8只大鼠。另取8只大鼠作为空白组。随后，对大鼠进行抑郁样行为测试，并采集脑脊液样本检测促炎细胞因子[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）]。采集血清样本检测与下丘脑-垂体-肾上腺轴（HPA轴）相关的蛋白质，包括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），以及葡萄糖代谢。从每组收集肠道内容物，进行肠道菌群的16S rRNA测序分析和SCFAs测序。结果表明，ZJJ不仅改善了DD大鼠的葡萄糖代谢（P<0.01），还减轻了抑郁样行为（P<0.05）和HPA轴功能亢进（P<0.05或P<0.01）。此外，它还改善了大脑中的神经炎症反应，脑脊液中促炎细胞因子显著减少（P<0.05或P<0.01）证明了这一点。此外，ZJJ改善了肠道菌群，使DD大鼠的肠道菌群类似于空白组，其特征是厚壁菌门丰度增加。ZJJ显著提高了SCFAs（乙酸、丁酸、戊酸和异戊酸）的水平（P<0.01）。因此，推断ZJJ可有效改善肠道菌群失调，调节SCFAs，从而改善DD患者的葡萄糖代谢紊乱和抑郁样行为。
