可可粉对DSS诱导的小鼠结肠炎的抑制作用及分子机制

Inhibitory Effect and Molecular Mechanism of Cocoa Powder on Dextran Sulphate Sodium (DSS)-induced Colitis in Mice

摘要:

利用C57BL/6小鼠连续饮用7 d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，低和高剂量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。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。

Abstract:

A mouse model of ulcerative colitis was established by feeding C57BL/6 mice continuously with 3% dextran sulfate sodium salt (DSS) for 7 days, and the anti-inflammatory effect of cocoa powder (CP) and its molecular mechanism were evaluated. Twenty mice were randomly divided into four groups: control group (conventional drinking water), 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 weight loss of the model group was increased, the colon length (6.89 cm) was significantly lower than that of the control group (9.85 cm), and the histopathological score (5.20) was significantly higher than that of the control group (0.60). In addition, the mRNA and protein levels of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β in intestinal tissues of mice were increased by 9.72 times, 7.08 times, 7.39 times and 0.93 times, 0.44 times, 0.52 times. Meanwhile, phosphorylation level of key protein p65 in NF-κB signaling pathway was also increased by 4 times and the phosphorylation level of protein IκBα increased 2.12 times, all the differences were 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 groups were significantly reduced, which were 8.16 cm and 9.19 cm, 3.20 and 2.00, respectively. The mRNA levels of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β were decreased by 0.64 times, 0.72 times, 1.05 times and 2.03 times, 2.27 times, 2.07 times, and the protein expression levels decreased by 0.22 times, 0.14 times, 0.18 times and 0.58 times, 0.37 times, 0.68 times, respectively, and the phosphorylation level of p65 and IκBα protein also decreased by 0.62 times ,2.07 times and 1.69 times, 2.19 times, respectively, all the differences were statistically significant (p < 0.05). In conclusion, CP can significantly ameliorate colitis induced by DSS in mice, partly by inhibiting the activation of NF-κB p65 signaling pathway.