槲皮素改善4-硝基喹啉-1-氧化物诱导小鼠食管癌作用机制研究

Study on the Mechanism of Quercetin Alleviating 4-nitroquinoline-1-oxide Induced Esophageal Cancer in Mice

目的 探究槲皮素缓解4-硝基喹啉-1-氧化物(4-NQO)饮水法诱导的食管癌的作用机制。方法 利用4NQO诱导食管癌小鼠模型,分为正常组、模型组、西药组(奥美拉唑+铝碳酸镁+吗丁啉)和槲皮素组。肉眼和显微镜观察槲皮素治疗后食管的病理变化;流式细胞仪检测小鼠脾脏Th17和Treg细胞的占比;酶联免疫吸附实验检测血清白介素10(IL-10)、白介素17(IL-17)、肿瘤坏死因子(TNF-α)的含量;Western Blotting检测PI3K、AKT、p-AKT的蛋白含量。结果 4NQO诱导的食管癌小鼠食管癌组织出现异常增生,槲皮素组增生程度减轻;相比模型组,槲皮素组Th17细胞升高,Treg细胞、IL-10、IL-17、TNF-α降低,Th17/Treg比例升高(P <0.05);Western Blotting结果显示,经槲皮素干预后,PI3K、AKT、p-AKT/AKT蛋白表达水平降低(P <0.05)。结论 槲皮素通过调节Th17/Treg平衡从而延缓4NQO诱导食管癌的进程。

Objective To investigate the mechanism of action of quercetin in alleviating 4-nitroquinoline-1-oxide(4-NQO) drinking method-induced esophageal cancer.Methods The 4NQO-induced esophageal cancer mouse model was utilized and divided into normal group,model group,western drug group(compound of omeprazole,magnesium aluminum carbonate and morpholine) and quercetin group.The pathological changes of esophagus after quercetin treatment were observed by naked eye and microscope;the percentage of splenic Th17 and Treg cells in mice were detected by flow cytometry;the levels of IL-10,IL-17 and TNF-α were detected by enzyme-linked immunosorbent assay;PI3K,AKT,p-AKT were detected by Western Blotting.Results 4NQO-induced esophageal carcinoma mice showed abnormal hyperplasia,and the degree of hyperplasia was reduced in quercetin group.Compared with model group,quercetin group increased Th17 cells,decreased Treg cells,IL-10,IL-17 and TNF-α,and increased Th17/Treg ratio.Western Blotting showed that the protein expression levels of PI3K,AKT,p-AKT/AKT were decreased after quercetin treatment.Conclusion Quercetin regulate Th17/Treg balance to delay the progression of esophageal cancer induced by 4NQO.