脾虚湿阻型痛风的肠道菌群结构及代谢物特征及其促进高尿酸血症形成的机制研究

批准号:
81803973
项目类别:
青年科学基金项目
资助金额:
21.0 万元
负责人:
孙静
依托单位:
学科分类:
H3103.证候基础
结题年份:
2021
批准年份:
2018
项目状态:
已结题
项目参与者:
谢志军、何志兴、胡长锋、李海昌、包洁、严瑶琦、胡姣姣
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中文摘要
痛风与嘌呤代谢紊乱和/或尿酸排泄减少所致的高尿酸血症直接相关。肠道菌群、肠粘膜上皮细胞分泌的黄嘌呤氧化酶和嘌呤分子是肠道尿酸生成的重要因素。我们研究发现,痛风患者脾虚湿阻型高达60.7%,痛风患者肠道微生物多样性较低、肠杆菌及乙酸、琥珀酸、葡萄糖等代谢物增多,表明痛风患者存在肠道菌群和代谢产物失衡。正常肠道菌群的功能属于中医脾胃功能范畴。脾虚湿阻可能加重痛风肠道菌群和代谢物失衡状态。因此,我们建立了“脾虚湿阻型痛风患者肠道菌群及代谢产物可增加肠液中黄嘌呤氧化酶、ATP等嘌呤分子,促进肠腔尿酸形成,并影响肠上皮细胞尿酸转运蛋白功能,从而促进高尿酸血症和痛风的发生发展”的假说。现拟从肠道菌群、肠道代谢产物与肠道粘膜上皮细胞之间的相互关系入手,以揭示脾虚湿阻型痛风肠道菌群结构及肠道代谢产物特征,并阐明其促进脾虚湿阻型痛风高尿酸血症形成的机制,力求为痛风的证候本质和病理机制研究提供新证据和新思路。
英文摘要
Gout is directly associated with hyperuricemia due to purine metabolic disorders or decreased uric acid excretion. Intestinal flora and xanthine oxidase and purine molecules secreted by intestinal mucosal epithelial cells are important factors in the production of intestinal uric acid. The intestinal microbial diversity of gout patients was low, while the content of Enterobacter (belonging to xanthine oxidase producing bacteria) and acetic acid, succinic acid, glucose and other metabolites increased. In physiological condition, the function of normal intestinal flora belongs to the theory of spleen and stomach of TCM. Spleen deficiency and dampness obstruction may lead to the imbalance of intestinal flora and metabolites in patients with gout. Therefore, we now establish the hypothesis that intestinal flora and metabolites of gout patients can increase the purine molecules such as xanthine oxidase and ATP in intestinal fluid and promote the formation of intestinal uric acid and affect the function of uric acid transporter in intestinal epithelial cells, thereby promote the occurrence and development of hyperuricemia and gout. Based on the relationship between intestinal flora, intestinal metabolites and intestinal mucosal epithelial cells, this project is aimed to reveal the intestinal flora structure and intestinal metabolites of gout with spleen deficiency dampness obstruction type and to clarify the mechanism of promoting the formation of hyperuricemia of gout with spleen deficiency and dampness obstruction type, which may provide new evidence and new ideas for the study of syndromes essence and pathological mechanism of gout.
肠道是尿酸排泄的重要通路,肠道中的产黄嘌呤氧化酶菌群及肠道粘膜上皮细胞分泌黄嘌呤氧化酶(Xanthione oxidase,XO)等生成尿酸的关键分子是肠道尿酸生成的重要因素。本项目拟揭示脾虚湿阻型痛风/高尿酸血症的肠道菌群结构及肠道代谢产物特征,并阐明及促进脾虚湿阻型痛风/高尿酸血症形成的机制。本项目研究结果初步阐明了健康人群、脾虚湿阻型痛风患者、非脾虚湿阻型痛风患者三组样本间菌群组成存在差异;脾虚湿阻型痛风患者粪便移植高尿酸血症大鼠的血尿酸升高,肠环液中尿酸和黄嘌呤氧化酶的浓度升高;脾虚湿阻型痛风患者粪便移植高尿酸血症大鼠的肠道菌群减少了有益菌群的丰度;脾虚湿阻型痛风患者粪便移植高尿酸血症大鼠模型可上调血清中13C标记尿酸钠含量,下调肠环液中13C标记尿酸钠含量;脾虚湿阻粪便肠环液和非脾虚湿阻粪便肠环液可上调Caco-2和SLC2A9+Caco-2细胞黄嘌呤氧化酶含量;脾虚湿阻型痛风患者粪便移植高尿酸血症大鼠肠环液可升高Caco-2和SLC2A9+Caco-2细胞黄嘌呤氧化酶含量,增强Caco-2细胞和SLC2A9+Caco-2细胞吸收尿酸能力。综上所述:脾虚湿阻型痛风患者肠道菌群可增加肠液中XO,促进尿酸在肠腔的形成增多,从而促进高尿酸血症和痛风的发生发展。本研究从肠道产XO菌群、肠粘膜细胞分泌XO入肠道形成的尿酸生成环境的角度,揭示痛风脾虚湿阻型的本质特征。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Effect of a Traditional Chinese Medicine Formula (CoTOL) on Serum Uric Acid and Intestinal Flora in Obese Hyperuricemic Mice Inoculated with Intestinal Bacteria.
中药方(CoTOL)对接种肠道细菌的肥胖高尿酸血症小鼠血清尿酸和肠道菌群的影响
DOI:10.1155/2020/8831937
发表时间:2020
期刊:Evidence-based complementary and alternative medicine : eCAM
影响因子:--
作者:Gao Y;Sun J;Zhang Y;Shao T;Li H;Wang M;Zhang L;Bian H;Wen C;Xie Z;Lv H
通讯作者:Lv H
DOI:--
发表时间:2021
期刊:Annals of Palliative Medicine
影响因子:--
作者:汪梅姣;张祎;张敏;李海昌;温成平;赵婷;谢志军;孙静
通讯作者:孙静
祛浊通痹方调控雌激素受体GPR30抑制CLGI以促进结肠ABCG2表达改善痛风/HUA的机制研究
- 批准号:82374393
- 项目类别:面上项目
- 资助金额:48万元
- 批准年份:2023
- 负责人:孙静
- 依托单位:
国内基金
海外基金
