矢车菊素-3,5-O-双葡萄糖苷改善五氟尿嘧啶诱导小鼠化疗性肠黏膜炎的效果初探
A PRELIMINARY STUDY ON THE EFFECT OF CYANIDIN-3,5-O-DIGLUCOSIDE ON 5-FLUOROURACIL INDUCED INTESTINAL MUCOSITIS IN MICE
范峻峰 1刘俊阳 2秦晓辉 3王可盈 2黄春想 2刘智强 3宋家乐4
作者信息
- 1. 中南大学湘雅二医院桂林医院,桂林 541002
- 2. 桂林医学院公共卫生学院,桂林 541199
- 3. 广西环境暴露组学与全生命周期健康重点实验室,桂林 541199
- 4. 桂林医学院公共卫生学院,桂林 541199;广西环境暴露组学与全生命周期健康重点实验室,桂林 541199
- 折叠
摘要
目的 探讨矢车菊素-3,5-O-双葡萄糖苷(cyanidin-3,5-O-diglucoside,C35G)对改善五氟尿嘧啶(5-FU,30 mg/kg)诱导化疗性小鼠肠黏膜炎作用机制.方法 将BALB/c雄性小鼠随机分成正常组、模型组、C35G组.以连续 4 d腹腔注射 5-FU诱导肠黏膜损伤小鼠模型,C35G低高剂量组连续 7 日分别灌胃C35G(50、150 mg/kg).末次给药后,CO2 处死小鼠,取血和结肠组织.采用酶联免疫吸附试法(ELISA)检测各组小鼠血清中肿瘤坏死因子(TNF-α)、白介素-1β(IL-1β)、白介素-10(IL-10)水平.苏木精-伊红(H&E)、过碘酸-雪夫(PAS)、阿利新蓝(Alcian Blue)染色观察各组小鼠结肠组织病理变化、杯细胞分布及黏蛋白 2(mucin2,MUC2)的分泌情况.Western blot 法检测结肠中Wnt、c-Myc蛋白表达水平.荧光实时定量PCR检测各组小鼠结肠组织中紧密连接蛋白mRNA表达水平.结果 与5-FU组相比,C35G处理能显著降低 5-FU造成的小鼠结肠肠黏膜损伤,并显著降低小鼠血清中TNF-α与IL-1β水平(P＜0.05),且升高IL-10 水平(P＜0.01).C35G能显著促进结肠组织中Wnt和c-Myc的蛋白表达,并显著提高紧密连接蛋白(Zo1、claudin1、claudin7、occludin)mRNA表达水平.结论 C35G对 5-FU诱导的小鼠化疗性肠黏膜炎具有明显改善作用.[营养学报,2024,46(2):146-154]
Abstract
Objective To explore the effect of cyanidin-3,5-O-diglucoside(C35G)on 5-fluorouracil(5-FU)-induced intestinal mucositis in mice.Methods BALB/c male mice were randomly divided into normal group,model group,low-dose and high-dose C35G groups.Except for the normal group,mice in other groups were treated with 5-FU to induce a mouse model of intestinal mucositis for 4 days.Mice in the C35G low-dose and high-dose groups were intragastrically administrated with C35G(50 and 150 mg/kg)for 7 consecutive days.Finally,all mice were euthanized,and blood and colon tissues were collected.The levels of TNF-α,IL-1β and IL-10 in the serum were detected by enzyme-linked immunosorbent assay(ELISA).HE,PAS,and alcian blue staining kits were used to stain the colon tissue sections,and the pathological changes of colon tissues,the content of goblet cells and the secretion of mucin 2 were observed.Western blot was used to detect the expression levels of Wnt and c-Myc in colon tissus.Real-time quantitative PCR was used to detect the expression levels of tight junction proteingenes.Results Compared with the 5-FU group,the preventive intervention of C35G could significantly reduce the colonic mucosal damages in mice exposed to 5-FU.In addition,C35G intervention could also significantly reduce the levels of TNF-α and IL-1β in the serum(P<0.05),increase the level of IL-10(P<0.01),and significantly increase the expression levels of Wnt and c-Myc in colon tissues.At the same time,the mRNA expression levels of tight junction proteins(Zo1,claudin1,claudin7,occludin)were significantly increased.Conclusion C35G is effective in ameliorating 5-FU-induced intestinal mucositis in mice.[ACTA NUTRIMENTA SINICA,2024,46(2):146-154]
关键词
矢车菊素-3,5-O-双葡萄糖苷/五氟尿嘧啶/肠黏膜损伤/炎症Key words
cyanidin-3,5-o-diglucoside/5-fluorouracil/intestinal mucosal damage/inflammation引用本文复制引用
基金项目
国家自然科学基金(81560530)
国家自然科学基金(81760589)
国家自然科学基金(81960590)
国家自然科学基金(82273630)
广西自然科学基金(2016GXNSFBA380172)
广西自然科学基金(2020GXNSFAA159160)
"西部之光"人才培养计划(2023)()
广西八桂青年拔尖人才支持计划(2023)()
人社部高层次留学回国人员资助计划(RSTH[2019]160)
出版年
2024
NETL
NSTL
万方数据