目的 基于miR-124-3p/白细胞介素-6（interleukin-6，IL-6）信号通路探究槲皮素与表儿茶素协同作用对炎症相关性结肠癌模型小鼠的干预作用及作用机制。方法 采用氧化偶氮甲烷（azoxymethane，AOM）/葡聚糖硫酸钠（dextran sodium sulfate，DSS）诱导小鼠建立炎症相关性结肠癌模型，同时单独或联合给予槲皮素和表儿茶素，待整个造模周期结束，测量各组小鼠结直肠长度，统计结直肠组织肿瘤数量；采用苏木素-伊红（HE）染色观察各组小鼠结肠组织病理变化；采用qRT-PCR检测结直肠组织中炎症相关基因[Toll样受体4（Toll-like receptor 4，TLR4）、IL-1β、IL-6、IL-17]及肿瘤相关基因[c-myc、血管内皮生长因子（vascular endothelial growth factor，VEGF）]和miR-124-3p的mRNA表达；采用Western blotting检测结直肠组织中磷酸化信号转导与转录活化因子3（phosphorylated signal transducer and activator of transcription 3，p-STAT3）和IL-6蛋白表达。结果 与对照组比较，模型组小鼠结直肠肿瘤浸润数量增加（P＜0.001），结直肠组织病理形态发生改变；结直肠组织中TLR4、IL-1β、IL-6、IL-17、c-myc和VEGF mRNA表达水平明显升高（P＜0.05），IL-6和p-STAT3蛋白表达水平明显升高（P＜0.01）。与模型组比较，给药组结直肠肿瘤浸润数量减少（P＜0.01、0.001），结直肠组织病理形态明显得到改善，且联合给药组作用优于单独给药组；结直肠组织中TLR4、IL-1β、IL-6、IL-17、c-myc和VEGF mRNA表达水平明显降低（P＜0.05、0.01），IL-6和p-STAT3蛋白表达水平明显降低（P＜0.05、0.01）。通过生物信息学预测发现miR-124-3p可靶向IL-6的3’-UTR序列，与对照组比较，模型组miR-124-3p表达降低（P＜0.05）；与模型组比较，各给药组miR-124-3p表达升高（P＜0.05）。结论 槲皮素联合表儿茶素通过miR-124-3p/IL-6的信号通路调节炎症反应，从而抑制结直肠癌。

Objective To explore the synergistic effect and mechanism of quercetin and epicatechin on inflammation-related colon cancer model mice based on miR-124-3p/interleukin-6 (IL-6) signal pathway.Methods The model of inflammation-related colon cancer was induced by azomethane (AOM)/dextran sodium sulfate (DSS) in mice, quercetin and epicatechin were administered alone or in combination. After the end of whole modeling cycle, colon length of mice in each group was measured and number of colorectal tumors were counted; The histopathological changes of colon tissue were observed by hematoxylin-eosin (HE) staining; Inflammation-related genes [Toll-like receptor 4 (TLR4), IL-1β, IL-6, IL-17], tumor-related genes [c-myc, vascular endothelial growth factor (VEGF)] and miR-124-3p mRNA expressions in colorectal tissue were detected by qRT-PCR; Western blotting was used to detect the expressions of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and IL-6 protein in colorectal tissue. Results Compared with control group, number of colorectal tumors infiltration in model group was increased (P < 0.001), pathological morphology of colorectal tissue was changed; TLR4, IL-1β, IL-6, IL-17, c-myc and VEGF mRNA expressions in colorectal tissue were significantly increased (P < 0.05), IL-6 and p-STAT3 protein expressions were significantly increased (P < 0.01). Compared with model group, number of colorectal tumor infiltration in treatment group were decreased (P < 0.01, 0.001), pathological morphology of colorectal tissue was significantly improved, and the effect of combined administration group was better than that of single administration group; TLR4, IL-1β, IL-6, IL-17, c-myc and VEGF mRNA expressions in colorectal tissue were significantly decreased (P < 0.05, 0.01), IL-6 and p-STAT3 protein expressions were significantly decreased (P < 0.05, 0.01). According to bioinformatics prediction, miR-124-3p could target the 3’-UTR sequence of IL-6. Compared with control group, miR-124-3p expression in model group was decreased (P < 0.05); Compared with model group, miR-124-3p expression in each treatment group was increased (P < 0.05). Conclusion Quercetin combined with epicatechin can regulate the inflammatory response through miR-124-3p/IL-6 signal pathway, thus inhibiting colorectal cancer.

R285.5

国家自然科学基金资助项目（81673675）