糖复康通过调节肠道菌群介导的APN-AMPK-BCAA信号通路对2型糖尿病发挥治疗作用
批准号:
82104812
项目类别:
青年科学基金项目(C类)
资助金额:
30.0 万元
负责人:
高慧娟
依托单位:
学科分类:
中医内科学
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
高慧娟
中文摘要
T2DM作为全球重点关注疾病,中药复方在其治疗中展现出良好的疗效,但由于缺乏合理的研究方法,中药复方作用机制研究陷入瓶颈。研究表明,肠道菌群紊乱影响BCAA合成、运输及分解代谢,导致T2DM的发生发展,而APN-AMPK是调控BCAA分解代谢的上游通路。前期研究显示,在T2DM中APN-AMPK-BCAA通路发生改变,糖复康通过APN-AMPK通路对T2DM发挥治疗作用。综上,本项目将重点研究“糖复康通过肠道菌群介导的APN-AMPK-BCAA信号通路对2型糖尿病发挥治疗作用”。具体拟开展以下内容:16s rDNA测序、粪菌移植实验,验证“肠道菌群是糖复康干预T2DM的关键靶点”。靶向代谢组学、分子生物学实验,验证“糖复康通过调节肠道菌群介导的APN-AMPK-BCAA信号通路对T2DM发挥治疗作用”,此研究结果将为中药复方作用机制研究提供新的思路。
英文摘要
T2DM is a global disease of focus, and TCM compounds show good efficacy in the treatment of T2DM. However, due to the lack of reasonable research methods, the research on the mechanism of action of TCM compounds is in a bottleneck. Studies have shown that intestinal flora disorders affect the synthesis, transportation and catabolism of BCAA, leading to the development of T2DM. APN-AMPK is an upstream pathway that regulates the catabolism of BCAA in host. Previous studies have shown that the APN-AMPK-BCAA pathway is changed in T2DM, and Tang-Fu-Kang plays a therapeutic role on T2DM through the APN-AMPK pathway. According to the above, this project will focus on the study of "the therapeutic effect of Tang-Fu-Kang on T2DM through the APN-AMPK-BCAA signaling pathway mediated by intestinal flora". Specifically, the following contents are proposed: 16s rDNA sequencing and fecal bacteria transplantation experiments to verify that "the intestinal flora is a key target for Tang-Fu-Kang intervention in T2DM"..Targeted metabolomics and molecular biology experiments verified that " Tang-Fu-Kang plays a therapeutic role on T2DM by regulating the APN-AMPK-BCAA signaling pathway mediated by intestinal flora", which will provide a new idea for studying the mechanism of action of TCM compounds.
T2DM作为全球重点关注疾病,中药复方在其治疗中展现出良好的疗效,糖复康作为临床治疗2型糖尿病气阴两虚证的有效方剂,其作用机制尚未揭示。本项目成功建立了KKAy糖尿病小鼠模型,并通过灌胃糖复康方进行了干预。研究结果表明,糖复康方显著改善了糖尿病小鼠的糖脂代谢紊乱,改善了肝脏和骨骼肌的病理变化,并修复了肠道黏膜屏障,降低糖尿病小鼠体内炎症因子水平。此外,糖复康方还显著调节了糖尿病小鼠的肠道菌群组成,恢复了菌群多样性和丰度,并显著提高了糖尿病小鼠体内脂联素(APN)含量,激活了肝脏及骨骼肌中AMPK-BCAA信号通路。本项目揭示了糖复康方通过APN-AMPK-BCAA信号通路治疗2型糖尿病的作用机制,并发现其对肠道菌群组成和多样性的显著调节作用。研究结果具有创新性,为中药复方治疗2型糖尿病提供了新的理论依据。
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海外基金