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彭岚玉,李定祥,姚敬心,罗政,邓奕辉.基于肠道菌群及其代谢产物SCFA探讨左归降糖通脉方对2型糖尿病大鼠糖脂代谢的影响[J].湖南中医药大学学报,2024,45(3):365-373[点击复制] |
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| 基于肠道菌群及其代谢产物SCFA探讨左归降糖通脉方对2型糖尿病大鼠糖脂代谢的影响 |
| 彭岚玉,李定祥,姚敬心,罗政,邓奕辉 |
| (湖南中医药大学, 湖南 长沙 410208) |
| 摘要: |
| 目的 基于肠道菌群及代谢产物短链脂肪酸（short-chain fatty acid， SCFA）探讨左归降糖通脉方（Zuogui Jiangtang Tongmai formula， ZJTF）干预2型糖尿病（type 2 diabetes mellitus， T2DM）的可能机制。方法 取12 只SD大鼠为空白（Control）组，喂食普通饲料；48只大鼠为造模组，以高脂饲料联合链脲佐菌素（streptozocin， STZ）制备T2DM模型。造模成功后随机分为模型（DM）组、ZJTF低剂量（ZJTF.L，12 g·kg-1）组、ZJTF高剂量（ZJTF.H，24 g·kg-1）组、二甲双胍150 mg·kg-1+阿托伐他汀10 mg·kg-1（M.A）组，药物干预4 周。监测大鼠精神状态、体质量与随机血糖；ELISA检测血清胰岛素（insulin， INS）、糖化血红蛋白（glycosylated hemoglobin， HbA1c）、炎症因子的水平；生化分析法检测血脂常规含量；HE染色观察结肠病理改变；16SrRNA观察肠道菌群结构；GC-MS检测血清SCFA水平。结果 与Control组比较，DM组出现多饮、多食、多尿、体质量减轻等症状；血糖、INS、HbA1c明显上升（P<0.01）；总胆固醇（total cholesterol， TC）、甘油三酯（triglyceride， TG）、低密度脂蛋白胆固醇（low density lipoprotein cholesterol， LDL-C）水平升高，高密度脂蛋白胆固醇（high density lipoprotein cholesterol， HDL-C）明显降低（P<0.01）；白细胞介素-1β（interleukin-1 β，IL-1β）、白细胞介素-6（interleukin-6， IL-6）及肿瘤坏死因子-α（tumor necrosis factor-α， TNF-α）水平均明显升高（P<0.01）；结肠固有层出现部分中断和消失，细胞肿胀、绒毛紊乱。DM组厚壁菌门和变形菌门、肠杆菌科、埃希菌-志贺菌属的相对丰度增加；血清乙酸、丁酸含量下降（P<0.05，P<0.01）。与DM组比较，ZJTF组血糖、INS、HbAlc均明显降低（P<0.05，P<0.01）；TC、TG、LDL-C明显降低，HDL-C明显升高（P<0.01）；IL-1β、IL-6及TNF-α水平明显降低（P<0.01）；结肠细胞肿胀及炎性浸润缓解；拟杆菌门和疣微菌门、乳酸菌科、阿克曼菌属丰度增加；血清丁酸、乙酸含量升高（P<0.05，P<0.01）。结论 左归降糖通脉方可能通过调节肠道菌群和SCFAs水平起到降血糖、稳血脂、减轻炎症反应的作用。 |
| 关键词: 左归降糖通脉方 2型糖尿病 肠道菌群 短链脂肪酸 糖脂代谢 |
| DOI：10.3969/j.issn.1674-070X.2024.03.004 |
| 投稿时间：2023-07-21 |
| 基金项目:湖南省教育厅科学研究项目（21A0228）；湖南省中医药科研计划项目（E2022010）；湖南中医药大学中西医结合一流学科开放基金项目（2020ZXYJH31）。 |
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| Effects of Zuogui Jiangtang Tongmai Formula on glucolipid metabolism in type 2 diabetic rats based on intestinal flora and its metabolite SCFA |
| PENG Lanyu,LI Dingxiang,YAO Jingxin,LUO Zheng,DENG Yihui |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To investigate the possible mechanism of Zuogui Jiangtang Tongmai Formula (ZGJTTMF) in the intervention of type 2 diabetes mellitus (T2DM) based on intestinal flora and short-chain fatty acid (SCFA) of the metabolites. Methods Twelve SD rats were selected as control group and fed with ordinary diet. Forty-eight rats were used as the modeling group, and a T2DM model was prepared by combining high-fat diet with streptozocin (STZ). After successful modeling, they were randomized into model (DM) group, low-dose (ZGJTTMF.L, 12 g·kg-1) and high-dose (ZGJTTMF.H, 24 g·kg-1) ZGJTTMF groups, and metformin 150 mg·kg-1+ atorvastatin 10 mg·kg-1 (M.A) group. Drug intervention lasted for 4 weeks. Mental state, body mass, and random blood glucose of rats were monitored. The levels of serum insulin (INS), glycosylated hemoglobin (HbAlc), and inflammatory factors were measured by ELISA. The routine content of blood lipid was determined by biochemical analysis. HE staining was used to observe the pathological changes of colon. The intestinal flora structure was observed by 16SrRNA. Serum SCFA levels were examined by GC-MS. Results Compared with control group, DM group showed symptoms such as polydipsia, polyphagia, polyuria, and decreased body mass. In addition, blood glucose, INS, and HbAlc significantly increased (P<0.01). Moreover, the levels of total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) increased, while high density lipoprotein cholesterol (HDL-C) significantly decreased (P<0.01). Besides, the levels of interleukin-1 β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) significantly increased (P<0.01). The lamina propria of the colon shows partial interruption and loss, with swelling cells and disordered villi. The relative abundance of Firmicutes and Proteobacteria, Enterobacteriaceae, and Escherichia Shigella increased in the DM group. In addition, the content of acetic acid and butyric acid in serum decreased (P<0.05, P<0.01). Compared with DM group, blood glucose, INS, and HbAlc in ZGJTTMF group significantly decreased (P<0.01). TC, TG, LDL-C also significantly decreased, while HDL-C significantly increased (P<0.01). The levels of IL-1β, IL-6, and TNF-α significantly decreased (P<0.01). Besides, colon cell swelling and inflammatory infiltration were relieved. The abundance of Bacteroidetes, Verrucobacteria, Lactobacillaceae, and Akkermansia increased. The content of butyric acid and acetic acid in serum increased (P<0.05, P<0.01). Conclusion ZGJTTMF may play a role in lowering blood glucose, stabilizing blood lipid, and alleviating inflammation by regulating intestinal flora and SCFA levels. |
| Key words: Zuogui Jiangtang Tongmai Formula type 2 diabetes intestinal flora short-chain fatty acid glucolipid metabolism |
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