目的 探讨清补凉汤通过调节 Th1/Th2/Th17/Treg 细胞平衡和肠道菌群对葡聚糖硫酸钠（DSS）诱导的溃疡 性结肠炎（UC）小鼠的治疗作用。方法 将 25 只 BALB/c 小鼠随机分为正常对照组、模型组、清补凉汤低剂量 组（0.6 g·kg-1 ）、清补凉汤高剂量组（1.2 g·kg-1 ）和清补凉汤对照组（1.2 g·kg-1 ），每组 5 只。通过在饮用水中连续 7 d 添加 3% DSS 复制溃疡性结肠炎小鼠模型。模型复制成功后按照设定剂量灌胃给药，每日 1 次，连续灌胃 给药 15 d。根据疾病活动指数（DAI）、结肠长度和病理评分评估小鼠的结肠炎症程度；实时荧光定量 PCR 法 检测干扰素 γ（IFN-γ）、白细胞介素 4（IL-4）、白细胞介素 17（IL-17）和叉头状转录因子 3（Foxp3）的 mRNA 表 达水平；采用 16SrDNA 基因高通量测序分析小鼠的肠道菌群变化。结果 与正常对照组比较，模型组小鼠体 质量显著下降（P＜0.001），DAI 评分显著升高（P＜0.001），结肠长度显著缩短（P＜0.001）；结肠病理组织可见 大量炎症细胞浸润黏膜及黏膜下层，隐窝被破坏，仅残留上皮细胞，病理评分显著增高（P＜0.001）；结肠组织 中的 INF-γ、IL-4 和 IL-17 的 mRNA 表达明显增高（P＜0.001），Foxp3 的 mRNA 表达呈下降趋势，但差异无统 计学意义（P＞0.05）；肠道菌群的优势种类数量减少，菌群丰度发生显著变化，在门的水平上 Firmicutes 丰度 显著降低，在属的水平上 Bacteroides、Parabacteroides 和 Flexispira 比例显著降低，S24-7 比例显著升高。与模 型组比较，清补凉汤低、高剂量组小鼠结肠显著增长（P＜0.001）；炎症浸润和组织损伤程度明显降低，病理评 分显著下降（P＜0.001）；其中清补凉汤低剂量组的 DAI 评分明显下降（P＜0.01），但清补凉汤高剂量组 DAI 评 分的差异无统计学意义（P＞0.05）；PCR 结果显示清补凉汤低剂量组的 INF-γ、IL-4 和 IL-17 的 mRNA 表达显 著下降（P＜0.05，P＜0.001），Foxp3 的 mRNA 表达显著上升（P＜0.001），但清补凉汤高剂量组的 INF-γ、 IL-4、IL-17 和 Foxp3 的 mRNA 表达差异均无统计学意义（P＞0.05）；肠道菌群在门的水平上显示清补凉汤低 剂量组小鼠的肠道菌群多样性和 Firmicutes 丰度明显增加，清补凉汤高剂量组 Firmicutes 丰度下降；在属的水 平上清补凉汤低、高剂量组小鼠的肠道菌群均显示有益菌 Akkermansia 比例显著升高。结论 清补凉汤对 DSS 诱导的溃疡性结肠炎小鼠具有治疗作用，其机制可能与调节 Th1/Th2/Th17/Tregs 细胞平衡及肠道菌群微生态相关。

Objective To investigate the therapeutic effects of Qingbuliang Decoction on dextran sulfate sodium （DSS） -induced ulcerative colitis （UC） in mice by regulating Th1/Th2/Th17/Treg cell balance and gut microbiota. Methods Twenty-five BALB/c mice were randomized into five groups （5 mice per group）：normal control，model，low-dose Qingbuliang Decoction （0.6 g·kg-1 ）， high-dose Qingbuliang Decoction （1.2 g·kg-1 ）， and Qingbuliang Decoction control （1.2 g·kg-1 ）. UC mice model was replicated by 3% DSS in drinking water for 7 consecutive days. After successful modeling，treatments were administered via gavage once daily for 15 days. Colonic inflammation severity was assessed using disease activity index （DAI），colon length，and histopathological scores. mRNA expression levels of interferon- γ（IFN-γ），interleukin-4（IL-4），interleukin-17（IL-17），and forkhead box protein 3（Foxp3） were measured by RT-qPCR. Gut microbiota alterations were analyzed via 16SrDNA high-throughput sequencing. Results Compared with the normal control group，the model group exhibited significant reductions in body mass （P＜0.001），markedly increased disease activity index （DAI） scores （P＜0.001），and shortened colon length （P＜0.001）. Histopathological evaluation revealed extensive inflammatory cell infiltration into the mucosa and submucosa，crypt destruction with only residual epithelial cells remaining，and significantly elevated histopathological scores （P＜0.001）. In colonic tissues， mRNA expression levels of IFN-γ，IL-4，and IL-17 were significantly upregulated （P＜0.001），while Foxp3 mRNA expression showed a downward trend without statistical significance （P＞0.05）. Gut microbiota analysis indicated a reduction in dominant species diversity and significant shifts in microbial abundance：at the phylum level，Firmicutes abundance decreased substantially， while at the genus level， proportions of Bacteroides， Parabacteroides， and Flexispira were significantly reduced，accompanied by a notable increase in S24-7. Compared with the model group， both low- and high-dose Qingbuliang Decoction groups demonstrated significantly elongated colons （P＜0.001）， reduced inflammatory infiltration and tissue damage severity， and decreased histopathological scores （P＜0.001）. Specifically， the low-dose group exhibited a significant decline in DAI scores （P＜0.01）， whereas the high-dose group showed no statistically significant difference in DAI scores （P＞0.05）. PCR results indicated that the low-dose group had significantly downregulated IFN-γ，IL-4，and IL-17 mRNA expression （P＜0.05，P＜0.001），alongside upregulated Foxp3 mRNA （P＜0.001）. In contrast，the high-dose group displayed no significant changes in mRNA expression of IFN-γ，IL-4，IL-17，or Foxp3（P＞0.05）. Gut microbiota analysis further revealed that at the phylum level，the low-dose group showed increased microbial diversity and elevated Firmicutes abundance，while the highdose group exhibited reduced Firmicutes abundance. At the genus level， both treatment groups demonstrated a significant increase in the proportion of the beneficial bacterium Akkermansia. Conclusion Qingbuliang Decoction alleviates DSS-induced UC in mice， potentially through modulating Th1/Th2/Th17/Tregs cell balance and gut microbiota homeostasis.

R285.5

国家自然科学基金面上项目（82174119）。