目的 研究菊苣酸对脓毒症小鼠肠损伤的影响及作用机制。方法 60只雄性C57小鼠随机分为对照组、模型组、地塞米松（5 mg/kg）组和菊苣酸高、中、低剂量（40、20、10 mg/kg）组，每组10只。各给药组ip相应药物3 d后，采用盲肠结扎穿孔手术（cecal ligation and puncture，CLP）诱导建立脓毒症小鼠模型。造模成功后连续给药48 h，采用苏木素-伊红（HE）染色观察小鼠肠组织病理变化；采用ELISA法测定肠组织中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-6（interleukin-6，IL-6）和IL-1β水平；取对照组、模型组和菊苣酸中剂量组的肠组织样本，基于Illumina测序平台进行转录组学分析；采用Western blotting检测肠组织Toll样受体9（Toll-like receptor 9，TLR9）、髓样分化因子88（myeloid differentiation factor 88，MyD88）、核因子-κB p65（nuclear factor-κB p65，NF-κB p65）、p-NF-κB p65和干扰素调节因子7（interferon regulatory factor 7，IRF7）蛋白表达。结果 与模型组比较，各给药组肠黏膜损伤程度明显改善，肠组织炎症因子水平均显著降低（P＜0.05、0.01）。转录组学分析显示，与对照组比较，模型组共分析出1140个差异表达基因；与模型组比较，给药组共分析出497个差异表达基因，差异基因均富集于NF-κB信号通路。与模型组比较，菊苣酸给药后肠组织TLR9、MyD88、p-NF-κB p65和IRF7蛋白表达水平均显著降低（P＜0.05、0.01）。结论 菊苣酸可通过TLR9/NF-κB信号通路改善脓毒症诱导的肠黏膜损伤。

Objective To study the effect and mechanism of chicory acid on intestinal injury in mice with sepsis. Methods Sixty male C57 mice were randomly divided into control group, model group, dexamethasone (5 mg/kg) group, cichoric acid high-, medium-, and low-dose (40, 20, 10 mg/kg) groups, with 10 mice in each group. The sepsis mouse model was induced by cecal ligation and perforation surgery (CLP) 3 d after ip administration to each group. After successful modeling, mice were continuously administered for 48 h, and HE staining was used to observe pathological changes in intestinal tissue; ELISA was used to detect levels of tumor crossing factor-α (TNF-α), Interleukin-6 (IL-6) and IL-1β in intestinal tissue; Intestinal tissue samples from control group, model group and cichoric acid medium-dose group were taken, and transcriptomic analysis based on Illumina sequencing platform was performed; Western blotting was used to detect expressions of Toll-like receptor 9 (TLR9), myeloid differentiation factor 88 (MyD88), nuclear factor-κB p65 (NF-κB p65), p-NF-κB p65 and interferon regulatory factor 7 (IRF7) proteins in intestinal tissue. Results Compared with model group, the degree of intestinal mucosal damage in each treatment group was significantly improved, and the levels of inflammatory factors in intestinal tissue were significantly reduced (P < 0.05, 0.01). Transcriptomics analysis showed that compared with control group, a total of 1140 differentially expressed genes were analyzed in model group; Compared with model group, a total of 497 differentially expressed genes were analyzed in administration group, all of which were enriched in NF-κB signaling pathway. Compared with model group, expressions of TLR9, MyD88, p-NF-κB p65 and IRF7 proteins in intestinal tissue after administration of cichoric acid were significantly reduced (P < 0.05, 0.01). Conclusion Chicory acid may ameliorate sepsis-induced intestinal mucosal injury through TLR9/NF-κB signaling pathway.

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国家科技重大专项重大新药创制项目（2017ZX09301058）；山东省自然科学基金青年项目（ZR2021QH111）；2022年全国名老中医药专家传承工作室建设项目（国中医药人教函[2022]75号）