目的 探讨槐绛方对溃疡性结肠炎（ulcerative colitis，UC）的治疗作用以及对NOD样受体热蛋白结构域3（NOD-like receptor family pyrin domain containing 3，NLRP3）/半胱氨酸蛋白酶-1（Caspase-1）通路的影响。方法 C57BL/6小鼠随机分为对照组、模型组以及槐绛方低、中、高剂量（0.2、0.4、0.8 g/kg）组，对照组给予正常饮用水，其余各组自由饮用3%葡聚糖硫酸钠（dextran sodium sulfate，DSS）水溶液诱导UC模型，连续7 d。造模同时各给药组灌肠不同剂量槐绛方，对照组和模型组灌肠等体积0.9%氯化钠溶液，每日记录各组小鼠体质量、便血、便形等症状改变，并进行疾病活动指数（disease activity index，DAI）评分，采用苏木素-伊红（HE）染色评估小鼠结肠黏膜组织病理改变，ELISA法检测结肠组织中白细胞介素-1β（interleukin-1β，IL-1β）和肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）水平，Western blotting法检测结肠组织中NLRP3、Caspase-1、Gasdermin D（GSDMD）蛋白表达。结果 与模型组比较，槐绛方明显减缓小鼠体质量下降，有效减轻小鼠结肠炎症状，降低炎症因子（TNF-α、IL-1β）和焦亡相关蛋白（NLRP3、cleaved Caspase-1、GSDMD-N）表达（P<0.05、0.01），对UC损伤有较好的改善作用，且呈剂量相关性。结论 槐绛方具有改善UC小鼠炎症状态、恢复结肠形态、抑制细胞焦亡作用，其作用机制与调控NLRP3/Caspase-1通路密切相关。

Objective To investigate the therapeutic effect of Huai Jiang Fang (槐绛方, HJF) on ulcerative colitis (UC) and explore its possible mechanism through NOD-like receptor family pyrin domain containing 3 (NLRP3)/Caspase-1 pathway. Methods C57BL/6 mice were randomized into control group, model group, low-, medium-and high-dose (0.2, 0.4, 0.8 g/kg) HJF groups. Mice in control group were given pure drinking water, and the rest groups were free to drink 3% dextran sodium sulfate (DSS) aqueous solution for 7 d to induce UC mice model. At the same time, mice in treatment group were pr administered with different doses of HJF, mice in control group and model group were pr administered with same dosage of saline solution. The changes of weight, hematochezia and stool shape were recorded. The pathology changes of colonic mucosa tissue were evaluated using HE staining. ELISA was carried out to detect the levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in colon tissue. Western blotting was used to detect the protein expressions of NLRP3, Caspase-1 and Gasdermin D (GSDMD) in colon tissue. Results Compared with control group, HJF significantly slow down the weight loss of mice, effectively alleviate colonic inflammatory symptoms. Inflammatory cytokines (IL-1β and TNF-α) levels and proteins associated with pyroptosis (NLRP3, cleaved caspase-1 and GSDMD-N) expressions in colon tissue were reduced by HJF (P<0.05, 0.01), which exhibited a beneficial therapeutic effect on UC with a dose-dependent manner. Conclusion HJF could improve the inflammatory state, restore colon morphology and inhibit cell pyroptosis in UC mice, and the possible mechanism may be closely related to the regulation of NLRP3/Caspase-1 pathway.

R285.5

湖北省卫生健康委员会2019—2020年度面上项目（WJ2019M070）；湖北省医学青年拔尖人才项目（EWT2019-48）