目的 明确葛根芩连汤对溃疡性结肠炎（ulcerative colitis，UC）的治疗作用，并阐明其是否通过靶向G蛋白偶联受体171（G protein-coupled receptor 171，GPR171）调控肠固有层CD4⁺ T细胞功能，从而发挥免疫调节效应。方法 在野生型（WT）C57BL/6小鼠中，采用葡聚糖硫酸钠（dextran sulfate sodium，DSS）诱导建立UC小鼠模型，设置对照组、模型组及葛根芩连汤低、中、高剂量（0.71、1.42、2.84 g/kg）组和美沙拉嗪（100 mg/kg）组，通过疾病活动指数（disease activity index，DAI）、结肠长度、组织病理学评分等评估其药效。进一步通过分子对接模拟葛根芩连汤主要活性成分与GPR171蛋白的结合能力。为深入探究分子机制，采用GPR171基因敲除（GPR171^-/-）小鼠及同背景WT小鼠，分别设置模型组与葛根芩连汤（1.42 g/kg）组，对比分析其一般状况、病理损伤、相关炎性因子表达、免疫细胞浸润以及肠固有层CD4⁺ T细胞亚群分化与细胞因子分泌情况。结果 在WT小鼠中，葛根芩连汤干预后小鼠DAI评分降低（P＜0.01、0.001），结肠长度增加（P＜0.05、0.001），组织病理损伤减轻，结肠组织中促炎因子肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（interleukin-6，IL-6）、IL-1β、IL-17A的mRNA表达水平显著下调（P＜0.05、0.01），抗炎因子IL-10的表达水平显著上调（P＜0.01）。分子对接提示葛根素、甘草苷等成分与GPR171具有高亲和力。与WT模型组比较，GPR171^-/-模型组小鼠肠道病理损伤更明显，结肠组织中CD4⁺ T细胞浸润及IL-17A表达水平显著升高（P＜0.001）。在GPR171^-/-小鼠中，葛根芩连汤干预后，小鼠的相对初始体质量、结肠长度、DAI评分与模型组相比均无显著改善，结肠组织中IL-17A⁺ CD4⁺ T细胞比例未见降低，IL-10⁺ CD4⁺ T细胞比例未见升高，且上述指标与WT葛根芩连汤组相比差异具有统计学意义（P＜0.001），表明葛根芩连汤对GPR171^-/-小鼠的治疗作用被显著削弱。结论 葛根芩连汤对UC的治疗作用可能为通过靶向GPR171，进而抑制CD4⁺ T细胞的促炎性功能极化（以降低IL-17A产生为特征），恢复肠道免疫稳态，减轻炎症与黏膜损伤。

Objective To investigate the therapeutic effect of Gegen Qinlian Decoction (葛根芩连汤, GQD) on ulcerative colitis (UC) and elucidate whether it exerts immunomodulatory effects by targeting G protein-coupled receptor 171 (GPR171) to regulate the function of CD4⁺ T cells in the intestinal lamina propria. Methods A UC mouse model was established in wild-type (WT) C57BL/6 mice using dextran sulfate sodium (DSS). The mice were divided into control group, model group, GQD low-, medium- and high-dose (0.71, 1.42, 2.84 g/kg) groups and mesalazine (100 mg/kg) group. The therapeutic efficacy was evaluated by disease activity index (DAI), colon length and histopathological score. Molecular docking was performed to predict the binding affinity of the main active components of GQD to GPR171. To further explore the molecular mechanism, GPR171 knockout (GPR171^-/-) mice and WT mice of the same background were used. They were divided into model group and GQD (1.42 g/kg) group. General condition, pathological injury, expressions of related inflammatory factors, immune cell infiltration, as well as differentiation and cytokine secretion profiles of CD4⁺ T cell subsets in the intestinal lamina propria were compared and analyzed. Results In WT mice, GQD significantly decreased DAI score (P < 0.01, 0.001), increased colon length (P < 0.05, 0.001), and alleviated histopathological damage. Meanwhile, the mRNA expression levels of pro-inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and IL-17A in colon tissue were significantly down-regulated (P < 0.05, 0.01), while the expression of anti-inflammatory factor IL-10 was significantly up-regulated (P < 0.01). Molecular docking suggested that components such as puerarin and liquiritin exhibited high affinity for GPR171. Compared with WT model mice, GPR171^-/- model mice showed more severe intestinal pathological damage, with significantly increased CD4⁺ T cell infiltration and IL-17A expression in colon tissue (P < 0.001). In GPR171^-/- mice, after GQD intervention, there were no significant improvements in relative initial body weight, colon length, DAI score compared with model group. The proportion of IL-17A⁺ CD4⁺ T cells in colon tissue did not decrease, and the proportion of IL-10⁺ CD4⁺ T cells did not increase. Moreover, the above indicators were significantly different from those in the WT GQD group (P < 0.001), indicating that the therapeutic effect of GQD was largely abolished in GPR171^-/- mice. Conclusion The therapeutic effect of GQD on UC may be achieved by targeting GPR171, thereby inhibiting the pro-inflammatory functional polarization of CD4⁺ T cells (characterized by reduced IL-17A production), restoring intestinal immune homeostasis, and alleviating inflammation and mucosal damage.

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国家自然科学基金青年项目（82305143）；国家自然科学基金青年项目（82505431）；国家自然科学基金青年科学基金经费配套项目（XPT82305143）；南京中医药大学“双百计划”（名老中医药专家学术经验继承项目）第一批（013062024003-22）；2025年省级大学生创新创业训练计划项目（S202510315007）