Jiang Congqiao, Zhu Pingsheng, Shi Yi, Xiang Wujun, Ge Sitang, Zhang Zongbing, Zuo Lugen
Department of Gastroenterology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2019 Jul 30;39(7):778-783. doi: 10.12122/j.issn.1673-4254.2019.07.05.
To investigate the protective effect of procyanidin B2 (PCB2) on the intestinal barrier and against enteritis in mice with trinitrobenzene sulphonic acid (TNBS)-induced colitis and explore the possible mechanism.
A mouse model of TNBS-induced colitis was established in male Balb/c mice aged 6-8 weeks. The successfully established mouse models were randomly divided into PCB2 treatment group (=10) and model group (=10) and were treated with daily intragastric administration of PCB2 (100 mg/kg, 0.2 mL) and 0.2 mL normal saline, respectively. After 4 weeks, the disease symptoms, intestinal inflammation, intestinal mucosal cell barrier function and the changes in PI3K/AKT signaling were evaluated using HE staining, immunofluorescence assay and Western blotting.
The disease activity index of the mice was significantly lower and the mean body weight was significantly greater in PCB2 group than in the model group in the 3rd and 4th weeks of intervention ( < 0.05). The levels of colonic inflammation and intestinal mucosal inflammatory mediators IL-1β and TNF-α were significantly lower while IL-10 was significantly higher in PCB2 group than in the model group ( < 0.05). Compared with those in the model group, the mice in PCB2 treatment group showed a significantly lower positive rate of bacterial translocation in the mesenteric lymph nodes and a lower thiocyanate-dextran permeability of the intestinal mucosa ( < 0.05). Western blotting showed that PCB2 treatment significantly increased the expressions of claudin-1 and ZO-1 ( < 0.05) and significantly lowered the expression levels of p-PI3K and p-AKT in the intestinal mucosa as compared with those in the model group ( < 0.05).
PCB2 suppresses intestinal inflammation and protects intestinal mucosal functions and structural integrity by inhibiting intestinal PI3K/AKT signaling pathway, suggesting the potential of PCB2 as a new drug for Crohn's disease.
研究原花青素B2（PCB2）对三硝基苯磺酸（TNBS）诱导的小鼠结肠炎肠道屏障的保护作用及抗肠炎作用，并探讨其可能机制。
在6-8周龄雄性Balb/c小鼠中建立TNBS诱导的结肠炎小鼠模型。将成功建立的小鼠模型随机分为PCB2治疗组（n = 10）和模型组（n = 10），分别每日灌胃给予PCB2（100 mg/kg，0.2 mL）和0.2 mL生理盐水。4周后，采用苏木精-伊红（HE）染色、免疫荧光分析和蛋白质印迹法评估疾病症状、肠道炎症、肠黏膜细胞屏障功能及PI3K/AKT信号通路的变化。
干预第3周和第4周时，PCB2组小鼠的疾病活动指数显著低于模型组，平均体重显著高于模型组（P < 0.05）。与模型组相比，PCB2组结肠炎症水平及肠黏膜炎症介质白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）水平显著降低，而IL-10水平显著升高（P < 0.05）。与模型组相比，PCB2治疗组小鼠肠系膜淋巴结细菌移位阳性率显著降低，肠黏膜硫氰酸盐-葡聚糖通透性降低（P < 0.05）。蛋白质印迹法显示，与模型组相比，PCB2治疗显著增加了紧密连接蛋白-1（claudin-1）和闭合蛋白（ZO-1）的表达（P < 0.05），并显著降低了肠黏膜中磷酸化磷脂酰肌醇-3激酶（p-PI3K）和磷酸化蛋白激酶B（p-AKT）的表达水平（P < 0.05）。
PCB2通过抑制肠道PI3K/AKT信号通路抑制肠道炎症，保护肠黏膜功能和结构完整性，提示PCB2作为治疗克罗恩病新药的潜力。
