目的:基于核因子E2相关性因子2（Nrf2）/胱氨酸/谷氨酸逆向转运蛋白溶质载体家族7成员11（SLC7A11）/谷胱甘肽过氧化酶4（GPX4）通路观察黄连厚朴汤（Huanglian Houpo Decoction，HLHPD）对溃疡性结肠炎（UC）模型小鼠的影响，并探讨其可能的作用机制。 方法:将60只小鼠随机分为6组：空白对照组、葡聚糖硫酸钠盐（DSS）模型组、西药柳氮磺吡啶组（西药组）以及黄连厚朴汤低（HLHPD‑L组）、中（HLHPD‑M组）、高（HLHPD‑H组）剂量组，每组10只，除空白组外，采用DSS建立UC模型。造模成功后，除空白组和模型组灌胃等体积蒸馏水外，HLHPD‑L组、HLHPD‑M组、HLHPD‑H组及西药组分别给予相应剂量黄连厚朴汤和柳氮磺吡啶（4 g/kg）药液灌胃，每天1次，连续给药14 d。观察小鼠一般情况、疾病活动指数；酶联免疫吸附实验检测各组小鼠血清白细胞介素IL‑6、IL‑1β及肿瘤坏死因子TNF‑α含量；试剂盒检测结肠组织中MDA、SOD、GSH的含量；通过H&E染色观察各组小鼠结肠组织病理变化；透射电子显微镜观察小鼠结肠组织超微结构；采用Western Blot检测小鼠结肠组织Nrf2、SLC7A11、GPX4蛋白表达情况。 结果:与空白对照组比较，DSS组小鼠疾病活动指数评分，血清中促炎症细胞因子IL‑6、IL‑1β和TNF‑α的表达水平，以及结肠组织中MDA水平显著上调，SOD、GSH水平明显降低（P<0.01）；各药物干预组上述炎症因子水平较DSS组降低（P<0.01），HLHPD中剂量组和高剂量组组织中MDA水平降低（P<0.01），SOD和GSH水平升高（P<0.05）；H&E染色结果显示，HLHPD可有效改善组织病理学损伤，减少组织坏死深度和范围；透射电镜结果显示，HLHPD各组肠黏膜、微绒毛及桥粒结构，以及肠上皮细胞间连接明显恢复；Western blot结果显示，DSS组小鼠结肠组织中Nrf2、GPX4、SLC7A11蛋白表达较空白对照组显著降低（P<0.01）；与DSS组比较，给黄连厚朴汤后，各剂量组Nrf2、GPX4、SLC7A11蛋白表达显著升高（P<0.01）。 结论:HLHPD可有效改善UC的炎症损伤，其作用机制可能与调控Nrf2/SLC7A11/GPX4通路介导的铁死亡有关。

Objective:To observe the effects of Huanglian Houpo Decoction （HLHPD） on ulcerative colitis （UC） model mice based on the nuclear factor E2‑associated factor 2 （Nrf2）/Cystine/Glutamate reverse transporter solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway， and to explore its possible mechanism of action. Methods:A total of 60 mice were randomly divided into 6 groups： the blank group， the model group （DSS group）， the Western medicine Sulfasalazine group， the low‑dose， medium‑dose and high‑dose HLHPD groups （HLHPD‑L， HLHPD‑M， and HLHPD‑H）， with 10 mice in each group. The UC model was established using dextran sulfate sodium salt （DSS） except the blank group. After the UC moldel was established， except for the blank group and the model group， which were administered equal volumes of distilled water via gavage， the HLHPD‑L， HLHPD‑M， HLHPD‑H， and Western medicine groups （4 g/kg） were given the respective doses of the HLHPD and drug by gavage once a day for 14 consecutive days. The general conditions and disease activity index of mice were observed. The concentrations of serum cytokines， including IL‑6， IL‑1β， and TNF‑α， were quantified using enzyme‑linked immunosorbent assay kits. The levels of MDA， SOD， and GSH were quantitatively analyzed in colonic tissue samples using standardized biochemical assays. Histopathological alterations in colonic tissues were observed through hematoxylin‑eosin （H&E） staining. Furthermore， transmission electron microscopy was utilized to examine the ultrastructural characteristics of colonic specimens. The protein levels of Nrf2， SLC7A11 and GPX4 in the colon tissue of mice was detected by Western Blot. Results:Compared to the blank group， the disease activity index， the serum levels of IL‑6， IL‑1β and TNF‑α， and MDA in colon tissue were significantly increased in the DSS group， while SOD and GSH contents were significantly decreased（P<0.01）. Compared to the DSS group， the serum levels of IL‑6， IL‑1β and TNF‑α in each drug intervention groups were decreased （P<0.01）， the MDA levels in colon tissue of the HLHPD‑M and HLHPD‑H were decreased （P<0.01）， while the SOD and GSH levels were increased （P<0.05）. H&E staining results showed that HLHPD could effectively improve the histopathological damage and reduce the depth and range of tissue necrosis. Transmission electron microscope results showed that the structure of intestinal mucosa， microvilli， desmosome， and the connections of intestinal epithelial cells recovered obviously. Western blot results revealed a statistically significant downregulation （P<0.01） in the protein expression levels of Nrf2， SLC7A11， and GPX4 in the DSS group when compared to the blank group. The protein expression levels of Nrf2， GPX4 and SLC7A11 in each group were significantly increased after administration of HLHPD （P<0.01） when compared to the DSS group. Conclusion:HLHPD can effectively improve the inflammatory injury of UC， and its mechanism may be related to the regulation of ferroptosis mediated by the Nrf2/SLC7A11/GPX4 pathway.

R285.5

河南省医学科技攻关计划（联合共建）项目（LHGJ20190273）；国家级大学生创新创业训练计划项目（202111834031）；大学生创新创业训练项目（2023xscxcy084）