【目的】 探讨知母多糖对经典热性药（附子、干姜和肉桂）联合、连续、长期给药模拟热证所致肠黏膜溃疡的治疗效 果，及其对肠道菌群的调节作用。【方法】 将 90只雄性 C57BL/6小鼠随机分为 6组，分别为空白组，模型组，三寒药（黄芩、 黄连、黄柏）组及知母多糖高、中、低剂量组。除空白组外，其余各组小鼠灌胃三热药（附子、干姜和肉桂）复制热证模型。 分组干预后，苏木精-伊红（HE）染色法观察结肠组织嗜铬细胞形态，免疫组织化学（IHC）法检测结肠组织中 5-羟色胺 （5-HT）、血管活性肠肽（VIP）表达水平，酶联免疫吸附分析（ELISA）检测结肠组织中5-HT、VIP、去甲肾上腺素（NE）、肾上 腺素（E）含量，采用 16S rRNA扩增子测序技术检测小鼠结肠组织中的菌群变化。【结果】 模型组小鼠出现行动活跃、攀爬频 繁、掉毛及粪便干硬等热证表现，表明造模成功。与空白组比较，模型组结肠组织中5-HT、VIP表达水平及含量均显著降 低（P＜0.01），NE和 E含量显著升高（P＜0.01）；与模型组比较，三寒药组及知母多糖高、中剂量组 5-HT、VIP表达水平及 含量均显著升高（P＜0.01），NE、E含量显著下降（P＜0.01），知母多糖低剂量组亦呈改善趋势（P＞0.05）。16S rRNA测序结 果显示：与空白组比较，模型组Observed species和Chao1指数显著降低（P＜0.01），Shannon指数降低（P＜0.05），Simpson指 数上升（P＞0.05）；与模型组比较，知母多糖高剂量组 Observed species、Chao1、Shannon 显著升高（P＜0.05 或 P＜0.01）， Simpson显著下降（P＜0.05）。【结论】 知母多糖可改善热证模型小鼠肠黏膜溃疡，文肯菌属可能是热证模型小鼠肠黏膜溃疡的 潜在标志菌属。

Objective To investigate the therapeutic effect of Anemarrhena polysaccharides on intestinal mucosal ulceration in mice induced by a classical heat-natured drug combination （Aconiti Lateralis Radix Praeparata， Zingiberis Rhizoma and Cinnamomi Cortex） administered jointly，continuously，and long-term to simulate a heat syndrome pattern， and to preliminarily explore its regulatory effect on gut microbiota. Methods Ninety male C57BL/6 mice were randomly divided into six groups：a blank control group，a model group，a three-cold-herbs （Scutellariae Radix，Coptidis Rhizoma，Phellodendri Chinesesis Cortex） group，and high-，medium-，and low-dose Anemarrhena polysaccharides groups. Except for the blank control group，mice in all other groups were orally administered the three-heat-herb （Aconiti Lateralis Radix Praeparata，Zingiberis Rhizoma and Cinnamomi Cortex） combination to replicate the heat syndrome model. Hematoxylin-eosin （HE） staining was used to observe chromaffin cell morphology in colon tissue. Immunohistochemistry （IHC） was employed to detect the expression levels of 5-hydroxytryptamine （5-HT） and vasoactive intestinal peptide （VIP） in colon tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the contents of 5-HT， VIP， norepinephrine （NE）， and epinephrine （E） in colon tissue. 16S rRNA amplicon sequencing was utilized to detect changes in the microbial flora within the mouse colon tissue. Results Mice in the model group exhibited manifestations of heat syndrome such as increased activity， frequent climbing， hair loss， and dry， hard feces， indicating successful model establishment. Compared with the blank control group，the expression levels and contents of 5-HT and VIP in the colon tissue of the model group were significantly decreased （P＜0.01）， while the contents of NE and E were significantly increased （P＜0.01）. Compared with the model group，the three-cold-herbs group and the high- and medium-dose Anemarrhena polysaccharides groups showed significantly increased expression levels and contents of 5-HT and VIP （P＜0.01） and significantly decreased contents of NE and E （P＜0.01）；the low-dose group also showed an improving trend （P＞0.05）. 16S rRNA sequencing results revealed that compared with the blank control group，the model group showed significantly decreased Observed species and Chao1 indices （P＜0.01），a decreased Shannon index （P＜0.05）， and an increased Simpson index （P＞0.05）. Compared with the model group， the high-dose Anemarrhena polysaccharides group exhibited significantly increased Observed species， Chao1， and Shannon indices （P＜0.05 or P＜0.01） and a significantly decreased Simpson index （P＜0.05）. Conclusion Anemarrhena polysaccharides can ameliorate intestinal mucosal ulceration in the heat syndrome mouse model. The Rikenella may be a potential biomarker genus for intestinal mucosal ulceration in heat syndrome model mice.

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黑龙江省自然科学基金项目（编号：LH2020H097）；无锡市“双百”中青年医疗卫生拔尖人才（编号：BJ2023072）；江苏省中医 退行性骨关节病临床医学创新中心资助项目；黑龙江省中医药管理局项目（编号：ZHY202088）