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[目的]以胰岛素信号通路中负调节蛋白PTP1B为靶点,筛选降糖药用真菌。[方法]比较了蛹虫草、蝙蝠蛾拟青霉、桑黄、灰树花4种药用真菌粗提物对PTP1B的抑制活性,并通过糖尿病小鼠模型进行验证。[结果]蝙蝠蛾拟青霉对PTP1B的抑制率最高,达到(78±2.81)%,其抑制类型为竞争性抑制。体内实验显示,蝙蝠蛾拟青霉降血糖效果最佳,小鼠空腹血糖降低了71.2%,与模型组有显著差异(p<0.01),和二甲双胍组相近。蛹虫草组、灰树花组和桑黄组血糖分别降低了62.7%、57.8%和48.3%。此外,各个实验组小鼠的甘油三酯、胆固醇、糖化血红蛋白和胰岛素水平与模型组也存在显著差异。[结论]PTP1B作为糖尿病的新靶标,在筛选降糖药用真菌的过程中也同样适用,而且蝙蝠蛾拟青霉显示了良好的降血糖活性。
[Objective] To screen the negative regulatory protein PTP1B in insulin signaling pathway to screen the hypoglycemic medicinal fungi. [Method] The inhibitory activities of four medicinal fungi extracts of Cordyceps militaris, bat moth Paecilomyces penicillata, Phellinus igniarius and Grifola frondosa on PTP1B were compared and verified by a mouse model of diabetes. [Result] The inhibitory rate of PTP1B in P. bat moth was the highest (78 ± 2.81)%, and its inhibitory type was competitive inhibition. The results of in vivo experiments showed that the blood glucose of Paecilomyces bat mom was the best, the fasting blood glucose of mice decreased by 71.2%, which was significantly different from the model group (p <0.01), similar to the metformin group. Cordyceps militaris group, Grifola frondosa and Phellin group blood glucose decreased by 62.7%, 57.8% and 48.3%. In addition, the levels of triglyceride, cholesterol, HbA1c, and insulin in each experimental group were also significantly different from those in the model group. [Conclusion] As a new target of diabetes, PTP1B is also applicable in the screening of hypoglycemic medicinal fungi, and the Paecilomyces bat mom shows a good hypoglycemic activity.