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基于肠道菌群及代谢组学研究丹酚酸A对糖尿病大鼠糖脂代谢的影响
徐金瑶,邹镇锴,李炫仪,邓洪敏,孙相钧,王旭锋,秦峰,阿布力克木·阿布力孜,陈乾,闫瑞承
湖北中医药大学第一临床学院武汉 430061;武汉市江夏区大桥中学武汉 430201;湖北中医药大学附属湖北省中医院胃肠外科武汉 430061;湖北中医药大学第一临床学院武汉 430061;湖北中医药大学附属湖北省中医院胃肠外科武汉 430061;中医肝肾研究及应用湖北省重点实验室湖北省中医院武汉 430061
摘要:
目的:基于肠道菌群和代谢组学探讨丹酚酸A治疗2型糖尿病(T2DM)的可能作用机制。方法:从30只SD大鼠随机选取8只为对照组,其余采用高脂饮食联合腹腔注射链脲佐菌素(35 mg/kg)建立T2DM大鼠模型。随机选取造模成功的16只大鼠均分为模型组、丹酚酸A组,丹酚酸A组采用丹酚酸A(1mg/kg)灌胃8周。进行大鼠葡萄糖耐量试验、胰岛素耐量试验,测定血清总胆固醇、甘油三脂、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇;16S rRNA高通量测序和液相色谱-串联质谱方法检测大鼠肠道菌群及肠道代谢物的变化。结果:与对照组比较,模型组在各时间点的血糖及糖耐量实验曲线下面积(AUC)显著升高(P <0.01),总胆固醇、甘油三脂、低密度脂蛋白胆固醇量显著升高(P <0.01);血清Chao1指数、ACE指数、Shannon指数降低,Clostridia、Lachnospirales、Clostridia_UCG-014、Lachnospiraceae、Muribaculaceae、Oscillospiraceae相对丰度下降,Bacilli相对丰度升高,Oscillospirales,Lactobacillaceae相对丰度升高(P <0.05);对照组与模型组差异代谢物有18种,模型组与丹酚酸A组有12种,三组之间共同差异代谢物有3种。与对照组相比,模型组甘氨脱氧胆酸、甘氨熊脱氧胆酸下调。结论:丹酚酸A对T2DM大鼠具有改善作用,其机制可能与调节肠道菌群、改变血清代谢物有关。
关键词:  丹酚酸A  2型糖尿病  肠道菌群  16S rRNA测序  代谢组学
DOI:10.3969/j.issn.1007-6948.2025.03.019
投稿时间:2024-08-19
基金项目:湖北省自然科学基金(联合基金项目)(2022CF142)
Effect of salvianolic acid A on glucose and lipid metabolism in diabetic rats based on intestinal flora and metabolomics
XU Jin-yao,ZOU Zhen-kai,LI Xuan-yi
Abstract:
Objective To explore the possible mechanism of salvianolic acid A in treating type 2 diabetes based on intestinal flora and metabolomics. Methods Eight out of thirty SD rats were randomly selected to serve as the normal control group, while the remaining rats were subjected to a high-fat diet in conjunction with intraperitoneal injections of streptozotocin (STZ, 35 mg/kg) to establish a type 2 diabetes mellitus (T2DM) rat model. The sixteen rats that successfully developed the model were then randomly divided into two groups: the model group and the salvianolic acid A group. The salvianolic acid A group received intragastric administration of salvianolic acid A (1mg/kg) for a duration of eight weeks. Subsequently, OGTT and ITT were performed on the rats, and serum levels of TC, TG, LDL-C and HDL-C were measured. Additionally, 16S rRNA high-throughput sequencing and liquid chromatography-tandem mass spectrometry methods were employed to assess changes in bacterial flora and intestinal metabolites in the rat intestines. Results Compared to the control group, the blood glucose levels and area under the curve (AUC) of the model group were significantly elevated at each time point (P <0.01). Additionally, serum levels of TC, TG and LDL-C were also significantly increased (P <0.01). Conversely, the serum Chao1 index, ACE index, and Shannon index were found to be decreased. The relative abundances of Clostridia, Lachnospirales, Clostridia_UCG-014, Lachnospiraceae, Muribaculaceae, and Oscillospiraceae were reduced, while the relative abundance of Bacilli, Oscillospirales, and Lactobacilaceae increased (P <0.05). A total of 18 distinct metabolites were identified between the control and model groups, with significant differences noted for salvianolic acid A. Among the groups, there were 12 types of metabolites identified, with 3 types classified as common differential metabolites across all three groups. In comparison to the control group, glycodeoxycholic acid and glycoursodeoxycholic acid were down-regulated in the model group. Conclusion Salvianolic acid A has an improving effect on T2DM rats, and its mechanism may be related to regulating intestinal flora and changing serum metabolites.
Key words:  Salvianolic acid A  type 2 diabetic  gut microbiota  16S rRNA gene sequencing  metabolomics analysis

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