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基于钙离子介导的COX-2/PGE2信号通路研究染料木黄酮缓解肠道损伤的作用机制
结题报告
批准号:
32002327
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
何阳
依托单位:
学科分类:
中兽医学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
何阳
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中文摘要
肠道健康是畜牧业生产性能和经济效益的重要保障。开发利用中兽药添加剂对畜牧业绿色健康和可持续发展具有重要意义。染料木黄酮是大豆异黄酮的主要活性物质,具有抗炎,抗氧化的多种生物功能。申请人前期研究表明染料木黄酮能够缓解由硫酸葡聚糖诱导或鼠伤寒沙门氏菌感染引起的结肠损伤。鉴于染料木黄酮具有调控细胞内钙离子浓度的潜在功效。本项目拟采用动物、细胞和类器官模型探讨染料木黄酮通过调控肠上皮细胞钙离子介导的COX-2/PGE2信号通路缓解肠道损伤的作用机制。通过检测细胞内钙离子浓度、COX-2的表达以及PGE2分泌,结合肠道上皮功能指标探究染料木黄酮抑制肠道损伤的分子机制。利用GPRC6A基因敲除小鼠及蛋白抑制剂调控细胞钙离子浓度及COX-2对该机制加以验证。本研究从钙离子调控的角度揭示染料木黄酮缓解肠道损伤的作用机制,为促进肠道健康的中药研发提供新的理论依据。
英文摘要
Gut health is an important guarantee for the production performance and economic benefits in livestock. The development and utilization of Chinese veterinary drug additives is of great significance to the green health and sustainable development of animal husbandry. Genistein is the main active substance of soybean isoflavones, which has various biological functions of anti-inflammatory and anti-oxidation. The applicant's previous studies have shown that genistein could relieve colon damage caused by dextran sulfateor Salmonella typhimurium infection. Given that genistein has the potential to regulate intracellular Ca2+ concentration. This project intends to use animal, cell, and organoid models to study the mechanism of genistein in alleviating intestinal damage by regulating COX-2/PGE2 signaling pathway mediated by Ca2+ in intestinal epithelial cells. Investigate the molecular mechanism of genistein in inhibition of intestinal damage by detecting intracellular Ca2+ concentration, COX-2 expression and PGE2 secretion and combining with intestinal epithelial function indicators. GPRC6A gene knockout mice and protein inhibitors were used to regulate the calcium concentration of cells and COX-2 to verify the mechanism. This study reveals the mechanism of genistein in inhibition of intestinal damage from the perspective regulation of Ca2+, and it provides a new theoretical basis for the research and development of Chinese medicine to promote intestinal health.
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DOI:10.1002/mnfr.202100209
发表时间:2021-06-29
期刊:MOLECULAR NUTRITION & FOOD RESEARCH
影响因子:5.2
作者:He, Yang;Ayansola, Hammed;Zhang, Bingkun
通讯作者:Zhang, Bingkun
国内基金
海外基金