目的 研究铁皮石斛多糖（Dendrobium officinale polysaccharide，DOP）对糖尿病前期（prediabetes，PDM）的作用，并从肠道短链脂肪酸（short chain fatty acids，SCFAs）-G蛋白偶联受体43（G-protein-coupled receptors 43，GPR43）-胰高血糖素样肽1（glucagon-like peptide 1，GLP1）信号通路探究其改善PDM的作用机制。方法 SD大鼠随机分为对照组、模型组和DOP低、高剂量（0.1、0.2 g/kg）组，每组10只。除对照组外，其余大鼠给予高糖高脂饮食喂养6周制备PDM大鼠模型，造模期间各给药ig相应药物，对照组和模型组ig等体积的蒸馏水。检测一般体征、血脂水平、血糖调节功能、肠和胰岛组织形态、粪便SCFAs含量、肠道和胰腺GPR43、GLP1及其受体表达等的变化。结果 与模型组比较，DOP显著增加PDM大鼠尾部微循环血流量（P＜0.01），显著降低肛温（P＜0.01），显著降低血清中总胆固醇、低密度脂蛋白胆固醇水平（P＜0.05、0.01），显著降低口服糖耐量、空腹血糖、餐后2 h血糖、胰岛素抵抗指数和C-肽水平（P＜0.05、0.01），增加胰岛素敏感指数，减轻胰腺、回肠及结肠病理损伤。气相色谱结果显示，DOP给药可显著增加粪便中乙酸、丁酸、异戊酸和总SCFAs水平（P＜0.05、0.01）。ELISA、Western blotting与qRT-PCR结果显示，DOP给药可增加显著血浆中GLP1水平和回肠、胰腺GPR43、GLP1受体mRNA和蛋白表达（P＜0.05、0.01）。结论 DOP可改善PDM，其作用可能与增加肠源性SCFAs，促进肠道和胰腺中GPR43表达，从而促进肠道GLP1分泌，修复β细胞功能，改善血糖调节功能有关。

Objective To investigate the effect of Dendrobium officinale polysaccharide (DOP) on prediabetes (PDM) and explore its mechanism in improving PDMs through the gut short-chain fatty acids (SCFAs)-G protein-coupled receptor 43 (GPR43)-glucagon-like peptide 1 (GLP1) pathway. Methods SD Rats were randomly divided into control group, model group and DOP low-, high-dose (0.1, 0.2 g/kg) groups, with 10 rats in each group. Except for the control group, the remaining rats were fed a high-sugar and high-fat diet for six weeks to establish a PDM model. During the modeling period, the corresponding drugs were administered intravenously, and the control group and model group were given distilled water of equal volume. Changes in general physiological indicators, glucose/lipid levels, glucose regulation function, intestinal/pancreatic histopathology, fecal SCFAs contents, expressions of GPR43 and GLP1 and its receptor in intestinal/pancreatic were analyzed. Results Compared with model group, DOP significantly increased tail microcirculatory blood flow in PDM rats (P < 0.01) and decreased anal temperature (P < 0.01), significantly reduced levels of total cholesterol and low-density lipoprotein cholesterol in serum (P < 0.05, 0.01), significantly decreased the oral glucose tolerance test results, fasting blood glucose, 2 h postprandial glucose, homeostasis model assessment-insulin resistance index, and C-peptide levels in PDM rats (P < 0.05, 0.01), increased the insulin sensitivity index (P < 0.05), and alleviated the pathological damage of pancreas, ileum and colon. Gas chromatography results showed that DOP administration could significantly increase the levels of acetic acid, butyric acid, isovaleric acid and SCFAs in feces (P < 0.05, 0.01). ELISA, Western blotting and qRT-PCR results showed that DOP administration could significantly increase the plasma GLP1 level, as well as the mRNA and protein expressions of GPR43 and GLP1 receptor in ileum and pancreas (P < 0.05, 0.01). Conclusion DOP could improve PDM, and its effect may be related to enhancing gut-derived SCFA production, up-regulating GPR43 expressions in intestine and pancreas, subsequent promoting GLP1 secretion, restoring β-cell function and improving glucose regulation.

R285.5

浙江省自然科学基金资助项目(LY24H280005);国家自然科学基金资助项目(81703772);浙江省重点实验室资助项目(2012E10002)