基于~1H NMR的代谢组学方法研究葛根芩连汤对高果糖诱导胰岛素抵抗大鼠粪便代谢组的影响（英文）
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摘要
研究表明过量高果糖摄入可诱导胰岛素抵抗(IR).葛根芩连汤(GQD)是临床常用的治疗2型糖尿病和胰岛素抵抗的中药之一,但其对果糖诱导的胰岛素抵抗的肠道菌群影响的相关研究甚少.本文采用基于核磁共振氢谱(~1H NMR)的代谢组学方法研究了GQD对高果糖诱导的胰岛素抵抗大鼠粪便代谢组的调控作用.通过连续8周给予大鼠10%果糖水喂养,成功建立胰岛素抵抗大鼠模型,GQD治疗组在果糖水喂养第5周至第8周同时给予GQD(18.2g/kg/day)灌胃.结果表明:与正常对照组相比,胰岛素抵抗模型组大鼠的饮水量、饮食量、体重和IR指数明显增加,空腹血糖值在第8周明显上升.在第8周末期,GQD治疗组的IR指数较胰岛素抵抗模型组显著降低,并且代谢紊乱得到改善:与胰岛素抵抗模型组相比,GQD治疗组胰岛素抵抗中丙酸、乙酸、琥珀酸、牛磺酸和甘油水平增加;而正丁酸、丙氨酸和谷氨酸的含量降低.这一结果表明GQD能够改善胰岛素抵抗所引起的大鼠氨基酸代谢、脂肪酸氧化和肠道微生物代谢等代谢紊乱状态.
Gegen Qinlian Decoction(GQD) is a commonly used traditional Chinese medicine formula for treating type 2 diabetes mellitus and insulin resistance(IR). The effects of GQD treatment on intestinal flora and its metabolism, however, are yet to be understood. In this study, the effects of GQD treatment on the fecal metabonome of high fructose-induced IR rats were investigated with a 1 H NMR-based approach. The IR model was established by feeding the rats with 10% fructose solution for 8 consecutive weeks. The animals in the GQD treatment group were gavaged with GQD daily(18.2 g/kg/day)from the 5 th to 8 th week. Compared with control group, The IR rats showed significantly increases in water/food intakes, body weight and IR index at the ends of the 4 th and 8 th week. The fasted plasma glucose(FPG) level of the IR rats increased by the end of the 8 th week. The GQD treatment lowered the IR index and normalized fecal metabonome by increasing the levels of propionate, acetate, succinate, taurine and glycerol, while decreasing the levels of n-butyrate, alanine and glutamate. These results indicated that the GQD treatment induced positive changes in amino acid metabolism, fatty acid oxidation and gut microbiota metabolism in the IR rats.
Gegen Qinlian Decoction(GQD) is a commonly used traditional Chinese medicine formula for treating type 2 diabetes mellitus and insulin resistance(IR). The effects of GQD treatment on intestinal flora and its metabolism, however, are yet to be understood. In this study, the effects of GQD treatment on the fecal metabonome of high fructose-induced IR rats were investigated with a 1 H NMR-based approach. The IR model was established by feeding the rats with 10% fructose solution for 8 consecutive weeks. The animals in the GQD treatment group were gavaged with GQD daily(18.2 g/kg/day)from the 5 th to 8 th week. Compared with control group, The IR rats showed significantly increases in water/food intakes, body weight and IR index at the ends of the 4 th and 8 th week. The fasted plasma glucose(FPG) level of the IR rats increased by the end of the 8 th week. The GQD treatment lowered the IR index and normalized fecal metabonome by increasing the levels of propionate, acetate, succinate, taurine and glycerol, while decreasing the levels of n-butyrate, alanine and glutamate. These results indicated that the GQD treatment induced positive changes in amino acid metabolism, fatty acid oxidation and gut microbiota metabolism in the IR rats.
引文
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[26]GUO Y,ZHANG Y C,HUANG W H,et al.Dose-response effect of berberine on bile acid profile and gut microbiota in mice[J].BMCComplement Altern Med,2016,16(1):394.
[27]NOH K,KANG Y,NEPAL M R,et al.Role of intestinal microbiota in baicalin-induced drug interaction and its Pharmacokinetics[J].Molecules,2016,21(3):337.
[28]AKAO T.Differences in the metabolism of glycyrrhizin,glycyrrhetic acid and glycyrrhetic acid monoglucuronide by human intes tinal flora[J].Biol Pharm Bull,2000,23(12):1418-1423.
[29]CHAO J,HUO T I,CHENG H Y,et al.Gallic acid ameliorated impaired giucose and lipid homeostasis in high fat diet-induced NAFLDmice[J].PloS One,2014,9(2):e96969.
[30]PAN S N,CHEN A L,HAN Z H,et al.1H NMR-based metabonomic study on the effects of Epimedium on glucocorticoid-induced osteoporosis[J].J Chromatogr B Analyt Technol Biomed Life Sci,2016,1038:118-126.
[31]ZHANG A H,SUN H,WANG Z G,et al.Metabolomics:towards understanding traditional Chinese medicine[J].Planta Med,2010,76(17):2026-2035.
[32]WANG X J,SUN H,ZHANG A H,et al.Potential role of metabolomics apporoaches in the area of traditional Chinese medicine:as pillars of the bridge between Chinese and western medicine[J].J Pharm Biomed Anal,2011,55(5):859-868.
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