利用C57BL/6小鼠连续饮用7 d 3%葡聚糖硫酸钠（DSS），建立溃疡性结肠炎模型，探讨可可粉（CP）的抗炎作用及机制。20只小鼠随机分成四组，对照组（常规饮水）、模型组（3% DSS饮水）及CP低、高剂量处理组（50、100 mg/(kg•d)灌胃加3% DSS饮水）。结果发现，与对照组相比，模型组小鼠体重丢失增多，结肠长度（6.89 cm）明显低于对照组（9.85 cm），而组织病理学评分（5.20）明显高于对照组（0.60）；同时，肠组织中促炎因子TNF-α、IL-6和IL-1β的mRNA和蛋白质表达水平分别增高了9.72、7.08、7.39倍和0.93、0.44、0.52倍，NF-κB信号通路关键蛋白p65的磷酸化水平增高了4倍，IκBα蛋白的磷酸化水平增高了2.12倍，差异均具有统计学意义（p<0.01）。与模型组相比，低、高剂量CP处理组小鼠体重丢失减少，结肠长度缩短明显减少，分别为8.16 cm和9.19 cm，组织病理评分分别降至3.20和2.00，促炎因子TNF-α、IL-6和IL-1β的mRNA表达水平分别降低了0.64、0.72、1.05倍和2.03、2.27、2.07倍，蛋白表达水平分别降低了0.22、0.14、0.18倍和0.58、0.37、0.68倍，p65蛋白和IκBα蛋白的磷酸化水平也分别降低了0.62、2.07倍和1.69、2.19倍，差异均具有统计学意义（p<0.05）。综上所述，CP对DSS诱导的小鼠结肠炎症有显著的抑制作用，其分子机制与抑制NF-κB p65信号通路活化有关。

A mouse model of ulcerative colitis was established through feeding C57BL/6 mice continuously 3% dextran sulfate sodium salt (DSS) for 7 days, to examine the anti-inflammatory effect of cocoa powder (CP) and its molecular mechanism. Twenty mice were randomly divided into four groups: control group (drinking water regularly), model group (3% DSS drinking water), and CP low and high dose treatment groups (50 and 100 mg/(kg•d) gavage plus 3% DSS drinking water). The results showed that compared with the control group, the model group lost more body weight, with its colon length (6.89 cm) significantly shorter than that of the control group (9.85 cm), and its histopathological score (5.20) significantly higher than that of the control group (0.60). In the meantime, the mRNA and protein expression levels of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β in the intestinal tissues of mice increased by 9.72 times, 7.08 times, 7.39 times and 0.93 times, 0.44 times and 0.52 times, respectively, while the phosphorylation levels of a key protein of the NF-κB signaling pathway, p65, and IκBα protein increased by 4 times and 2.12 times, respectively, with the differences being statistically significant (p<0.01). Compared with the model group, the weight loss, colon length and histopathological score of the low-dose and high-dose CP-treated groups were significantly reduced, with the colon lengths and histopathological scores being 8.16 cm and 9.19 cm, and 3.20 and 2.00, respectively. The mRNA expression levels of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β decreased by 0.64, 0.72 and 1.05 times, and 2.03, 2.27 and 2.07 times, respectively, the protein expression levels decreased by 0.22, 0.14 and 0.18 times, and 0.58, 0.37 and 0.68 times, respectively, and the phosphorylation levels of p65 and IκBα proteins decreased by 0.62 and 2.07 times, and 1.69 and 2.19 times, respectively. All the differences were statistically significant (p<0.05). In summary, CP exhibited a significant inhibitory effect against DSS-induced colitis in mice, and its molecular mechanism was related to the inhibition of NF-κB p65 signaling pathway activation.

国家自然科学基金项目（81703207）；江苏省高等学校大学生实践创新训练计划课题（202010313069Y）