基于“健脾消食”功效的传统发酵红曲的物质基础及作用机制研究

Red yeast rice is fermented by inoculating with Monascus on rice. Its effect was recorded in “Compendium of Materia Medica” that red yeast rice can promote digestion and improve blood circulation. At present, red yeast rice is fermented by pure culture. But the strain screening, process optimization and quality evaluation is only basd on the content of statins, which have the hypolipidemic effects. It is difficult to reflect the character of traditional Chinese medicine. Currently, the active substances base and related mechanisms of “Jianpixiaoshi” in red yeast rice are still not clear.Our preliminary experiment compared the composition differences between traditional fermentation Monascus and pure culture fermentation Monascus, and indicated that the content of statins in traditional fermentation Monascus was far below in the pure culture fermentation Monascus. So we analyzed that the material basis of “Jianpixiaoshi” in traditional fermentation Monascus are other substances except statins.In our project, we pay close attention to the sugars in the traditional fermentation, study the effect of Monascus on the rice starch modification and degradation, and analyze the transformation of sugars in the traditional fermentation. The active ingredients of sugar screening go through the rat model of Pi-qi-deficiency.It is investigated the gastrointestinal motility, morphology, hormones and the alteration of gut microbiota to reveal the mechanism of “Jianpixiaoshi” treatment with active ingredients of sugar in-depth study. Our project can provide the basis to clarify scientific connotation of the principle of “Jianpixiaoshi” in traditional fermentation Monascus.

红曲由红曲霉属真菌接种于稻米发酵而成。《本草纲目》中记载红曲功效为“健脾消食、活血化瘀”。目前红曲多为单一菌种的纯种发酵，其菌种筛选、发酵工艺优化、质量评价却“过度强调”降脂成分洛伐他汀，难以体现红曲作为传统中药的特色。而传统发酵红曲“健脾消食”的物质基础和作用机制尚不明确。课题组前期对比依据古法炮制的传统发酵红曲，与现代纯种发酵红曲的化学成分区别时，发现传统发酵红曲他汀类成分远低于纯种发酵红曲，分析传统发酵红曲“健脾消食”的物质基础为非他汀类成分。本项目关注非他汀的糖类物质，研究在传统发酵炮制过程中，红曲霉菌对稻米淀粉的改性及降解作用，分析红曲传统发酵过程中糖类物质的转化。并通过脾虚食积证大鼠模型，筛选能调节胃肠功能的活性糖类物质，从胃肠动力、胃肠组织形态、胃肠激素水平和肠道菌群方面深入探讨糖类有效成分治疗脾虚食积证的作用机制，阐明传统发酵红曲“健脾消食”的科学内涵。

红曲由红曲霉属真菌接种于稻米发酵而成，是一种食疗兼备的传统中药。在《本草纲目》中记载红曲的药用功能为“健脾消食、活血化瘀”。目前红曲发酵的菌种筛选、工艺优化、质量评价却“过度强调”降脂成分Monacolin K，难以体现红曲作为传统中药的特色。而红曲“健脾消食”的物质基础和作用机制尚不明确。本论文研究传统发酵红曲“健脾消食”的物质基础和作用机制，有助于阐明红曲发酵炮制的科学内涵，为曲类中药的共有性质“健脾消食”机理探索提供新的思路与借鉴。本项目研究表明红曲发酵过程中，糖类成分含量呈动态变化，并存在糖类成分的转化，发酵过程中红曲霉菌将大米中的淀粉转化为多糖和低聚糖。本项目采用“冰水灌胃+饮食不节”复合法建立脾虚食积证小鼠模型，并根据传统发酵红曲淀粉、可溶性多糖、低聚糖对脾虚食积证模型小鼠行为学、胃肠动力和胃液分泌等的调节作用，筛选出能调节胃肠功能的活性糖类成分，确定传统发酵红曲糖类成分治疗脾虚食积证的物质基础。本项目研究表明，传统发酵红曲中可溶性多糖可以显著恢复脾虚食积证小鼠的体重、进食量和排便量，增强胃肠动力，调节胃液pH及总酸度，升高血清胃蛋白酶水平，并且显著优于红曲低聚糖和红曲淀粉，故传统发酵红曲中可溶性多糖是治疗脾虚食积证的的物质基础之一。传统发酵红曲可溶性多糖调节脾虚食积证小鼠胃肠功能的机制可能为改善胃肠组织形态、调节胃肠激素、恢复肠道菌群结构、调节脾虚食积证小鼠胃窦平滑肌组织CNP-NPR-B-cGMP通路促进胃动力，以治疗脾虚食积证。