基于miR-29b调节SP1/IL-10促进肠道粘膜慢性炎症探讨痛泻要方对D-IBS合并T2DM患者肝郁脾虚证疗效的机制研究

批准号:
81904166
项目类别:
青年科学基金项目
资助金额:
20.0 万元
负责人:
陶文华
依托单位:
学科分类:
H3108.中医内科学
结题年份:
2022
批准年份:
2019
项目状态:
已结题
项目参与者:
--
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中文摘要
D-IBS患者中T2DM发病率高是临床亟待解决的难题。目前认为肠道黏膜慢性炎症是D-IBS和T2DM发病的重要机制之一。前期研究提示miR-29b调节sp1/IL-10为D-IBS合并T2DM肠道黏膜炎症反应发生的潜在关键节点。有研究报道健脾中药可减轻肠道黏膜局部炎症反应,在此基础上,本研究拟对180例D-IBS合并T2DM肝郁脾虚证患者用痛泻要方干预前后miR-29b与相关炎症因子相互作用机制的随机、对照的临床研究,在整体及基因水平上,分别建立证侯和方药效应的生物表征模型,探索:① D-IBS合并T2DM患者肝郁脾虚证与炎症反应相关性,miR-29b如何调节sp1/IL-10促进肠道黏膜慢性炎症反应;②疏肝健脾中药是否是通过影响miR-29b调节转录因子参与炎症反应机制实现的?从而揭示古方作用新靶点,为中医中药攻克D-IBS合并T2DM难题开辟新路子。
英文摘要
Given the higher type 2 diabetes mellitus (T2DM) occurrence in patients with diarrhea-predominant irritable bowel syndrome (D-IBS) is a serious trouble in clinic. Chronic intestinal mucosal inflammation is considered one of the important mechanisms of D-IBS and T2DM at present. Our previous studies have suggested that miR-29b regulates Sp1 / IL-10 as a potential key node in the intestinal mucosal inflammatory response of D-IBS combined with T2DM. Some studies have reported that Jianpi herbs can reduce intestinal mucosal local inflammatory response, on this basis, we take the most common syndrome in patients with D-IBS complicated T2DM, the liver depression and spleen deficiency syndrome as a starting point, a randomized, controlled clinical study on the mechanism of interaction between miR-29b and related inflammatory factors in 180 D-IBS patients with T2DM liver depression and spleen deficiency syndrome before and after treatment with traditional Chinese medicine, from the levels of clinic, animal and molecular cell to explore:①The correlation between the liver depression and spleen deficiency syndrome and inflammatory response;how miR-29b regulates sp1 / IL-10 in the pathogenesis of D-IBS with T2DM;②The mechanism of reduction the inflammatory response of Shuganjianpi herbs may reveal new targets of ancient prescriptions. And it is expected to make the TCM syndrome objective and to open a new way to overcome the high recurrence rate of this disease by TCM.
D-IBS患者中T2DM发病率高是临床亟待解决的难题。目前认为肠道黏膜慢性炎症是D-IBS和T2DM发病的重要机制之一。前期研究提示miR-29b调节sp1/IL-10为D-IBS合并T2DM肠道黏膜炎症反应发生的潜在关键节点。有研究报道健脾中药可减轻肠道黏膜局部炎症反应,在此基础上,本研究拟对163例D-IBS合并T2DM肝郁脾虚证患者用痛泻要方干预前后miR-29b与相关炎症因子相互作用机制的随机、对照的临床研究,研究表明痛泻要方可明显降低患者肠道症状积分,改善心理状况,提高生活质量。药物干预后患者血浆miR-29b表达降低, SP1mRNA表达升高,IL-10表达水平明显升高。动物研究从体内和体外探究TXYF对D-IBS合并T2DM大鼠的治疗作用和机制,研究表明TXYF干预后,claudin-1蛋白表达升高,结肠粘膜水肿减轻,从而降低D-IBS合并T2DM肝郁脾虚型大鼠的炎症反应。同时,进一步拓展研究发现TXYF可以通过调节氧化应激来调控RAGE蛋白通路,从而降低D-IBS合并T2DM肝郁脾虚型大鼠的炎症反应。体外研究表明,含药血清干预过表达miR-29b细胞后IL-10、 claudin-1、SP1表达明显升高。体内外研究表明,痛泻要方可通过降低miR-29b调节SP1/IL-10改善肠道粘膜慢性炎症,揭示古方作用新靶点,为中医中药攻克D-IBS合并T2DM难题开辟新路子。项目资助发表高质量论文3篇,其中一篇影响因子6.5,协助培养硕士生1名。项目投入经费20万元,支出17.733608万元,各项支出基本与预算相符。剩余经费2.266392万元,剩余经费计划用于本项目研究后续支出。
期刊论文列表
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专利列表
DOI:10.3760/cma.j.cn112309-20191111-00374
发表时间:2020
期刊:中华微生物学和免疫学杂志
影响因子:--
作者:瞿旻晔;陶文华
通讯作者:陶文华
Traditional Chinese medicine Tongxie Yaofang treating irritable bowel syndrome with diarrhea and type 2 diabetes mellitus in rats with liver-depression and spleen-deficiency: A preliminary study.
中药痛泻要方治疗肝郁脾虚型肠易激综合征腹泻并2型糖尿病大鼠的初步研究
DOI:10.3389/fnut.2022.968930
发表时间:2022
期刊:FRONTIERS IN NUTRITION
影响因子:5
作者:Xu, Weidong;Zhang, Zhiyi;Lu, Ye;Li, Mengxi;Li, Jiayao;Tao, Wenhua
通讯作者:Tao, Wenhua
国内基金
海外基金
