【作者】 孟迎； 顿孟倩； 刘芯源； 陈伟博； 张钟铭； 卢圣玉； 张国英； 凌建亚；

【Author】 Meng Ying;Dun Mengqian;Liu Xinyuan;Chen Weibo;Zhang Zhongming;Lu Shengyu;Zhang Guoying;Ling Jianya;State Key Laboratory of Microbial Technology,Shandong University;School of Pharmacy,Shandong University of Traditional Chinese Medicine;

【机构】 山东大学微生物技术研究院； 山东中医药大学药学院；

【摘要】 二型糖尿病合并非酒精性脂肪肝是临床常见的合并症之一,目前暂未开发出有效的治疗药物。蛹虫草是一种药食两用真菌,含有虫草素、虫草多糖等多种活性物质,具有广泛的药用价值。本研究以蛹虫草水提物及虫草素为研究对象,从肠道菌群-肝脏代谢的角度出发,深入探讨蛹虫草对二型糖尿病合并非酒精性脂肪肝的治疗效果及作用机制。我们利用高果糖高脂饲料联合腹腔注射STZ,成功构建了二型糖尿病合并非酒精性脂肪肝小鼠模型,蛹虫草及虫草素干预治疗后,合并症小鼠血糖和血脂降低,胰岛素抵抗减弱,糖脂代谢有所恢复。同时,蛹虫草及虫草素干预减轻肝脏脂质负担、改善肝损伤、减轻肝脏炎症、提高机体抗氧化水平。组学分析发现,蛹虫草及虫草素对合并症小鼠的肠道菌群、肝脏代谢物谱均有显著影响。多组学关联分析显示,肠道差异菌群与肝脏差异代谢物具有显著相关性,说明蛹虫草可以通过"肠道菌群-肝脏代谢"改善二型糖尿病合并非酒精性脂肪肝。更多还原

【Abstract】 Type 2 diabetes mellitus(T2DM) combined with non-alcoholic fatty liver(NAFLD) is one of the common clinical comorbidities for which no effective therapeutic drugs have been developed.Cordyceps militaris is a kind of medicinal and edible fungus,containing cordycepin,cordyceps polysaccharides and other active substances,which has a wide range of medicinal value.In this study,we took the Cordyceps militaris water extract and cordycepin as the research object,and explored the therapeutic effect and mechanism of action on T2DM combined with NAFLD in-depth from the perspective of intestinal flora-hepatic metabolism.We successfully constructed a mouse model of T2DM combined with NAFLD by using high fructose and high fat feed combined with intraperitoneal injection of STZ.After the intervention of Cordyceps militaris water extract and cordycepin,the blood glucose and blood lipids were reduced in mice with comorbidities,insulin resistance was weakened,and glucose-lipid metabolism was restored.Meanwhile,Cordyceps militaris water extract and cordycepin intervention reduced the liver lipid burden,improved liver injury,reduced liver inflammation,and increased the antioxidant level of the organism.Histological analysis revealed that Cordyceps militaris water extract and cordycepin had significant effects on the intestinal flora and liver metabolite profiles of mice with comorbidities.Multi-group correlation analysis showed that there was a significant correlation between different intestinal flora and significant liver metabolites,indicating that Cordyceps militaris could improve type 2 diabetes mellitus combined with NAFLD through "intestinal flora-liver metabolism".更多还原