【摘要】 目的 研究蒲黄炭纳米类成分（Typhae Pollen Carbonisatum nano-components,TPC-NCs）对溃疡性结肠炎（ulcerative colitis,UC）的治疗作用及其作用机制。方法 通过透析法从蒲黄炭水煎液中纯化出TPC-NCs，并利用纳米材料表征技术对其形态、光学特性及表面官能团进行表征。采用葡聚糖硫酸钠（dextran sodium sulfate,DSS）诱导建立UC小鼠模型，将30只C57BL/6J小鼠随机分为对照组、模型组、柳氮磺吡啶（sulfasalazine,SASP）组、TPC-NCs组和透析袋外溶液（TPC-O）组。连续给药7 d后，观察小鼠一般情况；评估小鼠疾病活动指数（disease activity index,DAI）；采用苏木素-伊红（hematoxylineosin,HE）染色观察结肠组织病理损伤；检测结肠组织髓过氧化物酶（myeloperoxidase,MPO）、超氧化物歧化酶（superoxide dismutase,SOD）活性及肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、IL-6、IL-2、IL-17A、IL-4、IL-10、丙二醛（malondialdehyde,MDA）水平；采用Western blotting检测结肠组织Toll样受体4(Tolllike receptor 4,TLR4)/髓样分化因子88(myeloid differentiation 88,MyD88)/核因子-κB(nuclear factor-κB,NF-κB)信号通路关键蛋白的表达。结果 TPC-NCs粒径集中在1.4～2.2 nm，分散性良好，表面富含羟基、羧基等官能团。体内实验结果显示，TPC-NCs能显著降低UC小鼠的DAI评分（P<0.01），改善结肠组织病理损伤，降低结肠组织MPO活性及MDA水平（P<0.01），提高结肠组织中抗氧化酶SOD活性（P<0.05），抑制促炎因子TNF-α、IL-1β、IL-6、IL-2、IL-17A释放（P<0.01），上调抗炎因子IL-4、IL-10水平（P<0.05、0.01），并降低结肠组织TLR4、MyD88、NF-κB p65的蛋白表达水平（P<0.05、0.01）。结论 TPC-NCs通过抑制TLR4/MyD88/NF-κB信号通路介导的炎症反应，减轻氧化应激损伤，从而发挥对UC的治疗作用。更多还原

【Abstract】 Objective To investigate the therapeutic effect and mechanism of Typhae Pollen Carbonisatum nano-components(TPCNCs) on ulcerative colitis(UC). Methods TPC-NCs were purified from the decoction of TPC via dialysis, their morphology, optical properties and surface functional groups were characterized using nanomaterial characterization techniques. A UC mouse model was established using dextran sodium sulfate(DSS), with 30 C57 BL/6J mice randomly divided into control group, model group, sulfasalazine(SASP) group, TPC-NCs group, and dialysis bag exterior solution(TPC-O) group. After 7 d of continuous administration, general mouse conditions were observed. Disease activity index(DAI) was evaluated. Hematoxylin-eosin(HE) staining was used to examine colonic histopathological damage. Myeloperoxidase(MPO) and superoxide dismutase(SOD) activities in colonic tissue, as well as tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), IL-6, IL-2, IL-17A, IL-4, IL-10 and malondialdehyde(MDA) levels were measured. Western blotting was employed to assess the expressions of key proteins in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB) signaling pathway in colon tissue. Results TPC-NCs exhibited particle sizes concentrated between 1.4—2.2 nm, with good dispersibility and abundant surface functional groups such as hydroxyl and carboxyl groups. In vivo experimental results demonstrated that TPC-NCs significantly reduced DAI score in UC mice(P < 0.01), improved colonic histopathological damage, decreased MPO activity and MDA level in colon tissue(P < 0.01), enhanced the antioxidant enzyme SOD activity in colonic tissue(P < 0.05), inhibited the release of pro-inflammatory factors TNF-α, IL-1β, IL-6, IL-2 and IL-17A(P < 0.01), upregulated the levels of anti-inflammatory factors IL-4 and IL-10(P < 0.05, 0.01), and reduced the protein expression levels of TLR4, MyD88 and NF-κB p65 in colon tissue(P < 0.05, 0.01). Conclusion TPC-NCs exert therapeutic effects on UC by mitigating oxidative stress damage through the suppression of TLR4/MyD88/NF-κB signaling pathway-mediated inflammatory response.更多还原