基于“脾胰同源”理论探讨薯蓣粥通过肠道菌群调控AMPK通路影响2型糖尿病大鼠糖脂代谢的作用机制

Regulation of host intestinal flora and its metabolite short-chain fatty acids through dietary intervention can activate AMPK energy metabolism pathway, target peripheral tissues, and improve insulin sensitivity, which is a new way to improve glucose and lipid metabolism in type 2 diabetes. Yam Gruel, a traditional Chinese medicine diet, is based on the theory of "Homogeny of Spleen and Pancreas", and follow the principle of “tonifying Qi of Spleen, and nourishing Yin of spleen”. Previous studies have confirmed that Yam Gruel can reduce blood sugar and blood lipids in T2DM patients, improve the growth of bifidobacteria in the intestine, and increase the content of short-chain fatty acids. As the above evidences showed, the clinical effect of Yam Gruel is significant, but the mechanism of how Yam Gruel to improve glucose and lipid metabolism of T2DM by regulating intestinal flora has not been clarified. Therefore, this study is intended to intervene the T2DM rat model by Yam Gruel, and then observe its effects on blood glucose, blood lipids and insulin secretion, and to explore the structure and abundance of intestinal flora and the short-chain fatty acid (SCFAs) in T2DM rats, which can activate AMPK pathway targeting muscle and liver tissue. The aim of this study is to interpret the mechanism of Yam Gruel in the treatment of glucose and lipid metabolic disturbance through gut microbiota activating AMPK pathway, and the results can provide theoretical support and new intervention strategy for clinical practice.

通过饮食干预调节宿主肠道菌群及其代谢产物短链脂肪酸，可激活AMPK能量代谢通路，靶向作用于外周组织，提高胰岛素敏感性，是改善2型糖尿病糖脂代谢的新途径。中医经典食疗方薯蓣粥是基于“脾胰同源”的理论，遵循“健脾益气，滋养脾阴”的原则所组方，前期研究证实薯蓣粥能够降低T2DM患者的血糖、血脂，促进肠道内双歧杆菌的生长，增加短链脂肪酸的含量，临床疗效显著，但薯蓣粥如何通过调节肠道菌群改善T2DM糖脂代谢的作用机制尚未明确。因此，本课题拟用薯蓣粥干预T2DM大鼠模型，观察其对T2DM大鼠血糖、血脂和胰岛素分泌的作用，并从“肠道菌群-SCFAs-AMPK”途径出发，探讨薯蓣粥对T2DM大鼠肠道菌群结构和丰度、代谢产物短链脂肪酸SCFAs的影响，以及靶向骨骼肌、肝脏AMPK通路的调节作用，从而阐明薯蓣粥在改善T2DM糖脂代谢的作用机制，为中医饮食调节T2DM糖脂代谢提供理论依据和新思路。

通过饮食干预调节宿主肠道菌群及其代谢产物短链脂肪酸，可激活AMPK能量代谢通路，靶向作用于外周组织，提高胰岛素敏感性，是改善2型糖尿病糖脂代谢的新途径。中医经典食疗方薯蓣粥是基于“脾胰同源”的理论，遵循“健脾益气，滋养脾阴”的原则所组方，前期研究证实薯蓣粥能够降低T2DM患者的血糖、血脂，促进肠道内双歧杆菌的生长，增加短链脂肪酸的含量，临床疗效显著，但薯蓣粥如何通过调节肠道菌群改善T2DM糖脂代谢的作用机制尚未明确。因此，本课题运用薯蓣粥干预T2DM大鼠模型，观察其对T2DM大鼠血糖、血脂和胰岛素分泌的作用，并从“肠道菌群-SCFAs-AMPK”途径出发，探讨薯蓣粥对T2DM大鼠肠道菌群结构和丰度、代谢产物短链脂肪酸SCFAs的影响，以及靶向骨骼肌、肝脏AMPK通路的调节作用，从而阐明薯蓣粥在改善T2DM糖脂代谢的作用机制。实验结果显示，薯蓣粥能有效降低T2DM模型大鼠的空腹血糖、血脂水平，提高胰岛素敏感性，缓解T2DM大鼠的肝功能异常和肝脏脂质积累,减轻糖尿病所引起的糖脂代谢紊乱。16S rRNA测序和气相色谱-质谱联用分析结果表明，薯蓣粥干预后能上调大鼠肠道菌群的在丰度和多样性指数,恢复肠道菌群结构，并上调代谢产物短链脂肪酸中乙酸、丙酸、丁酸的浓度。同时，薯蓣粥干预后骨骼肌的p-AMPK/AMPK，GLUT-4蛋白及mRNA表达显著增加，肝脏中p-ACC/ACC, p-AMPK/AMPK, MLYCD和CPT-1的蛋白表达水平显著升高。本研究证实了薯蓣粥能通过调节肠道菌群及其代谢物，靶向激活骨骼肌和肝脏的AMPK通路，提高胰岛素敏感性，改善T2DM大鼠的糖脂代谢，为中医饮食治疗2型糖尿病的中医饮食治疗及临床推广应用提供证据支撑和新思路。