基于“肺与大肠相表里”从SP-D表达及相关信号通路功能状态探索燥邪致病的分子机制
批准号:
82060827
项目类别:
地区科学基金项目
资助金额:
34.0 万元
负责人:
史红
依托单位:
学科分类:
证候基础
结题年份:
2024
批准年份:
2020
项目状态:
已结题
项目参与者:
史红
中文摘要
西北燥证是我国干旱半干旱区燥邪所致之复合型中医证候,罹患该证是西北地区人群亚健康及常见病的诱因和加重因素,探索燥邪致病机制有助于科学防治燥证。项目前期已建立并验证燥邪实验室模拟方案,使秋燥与西北燥邪微观致病机制的比较研究成为可能;证实了燥邪引发肺、气道SP-D表达增强、机体细胞免疫功能亢进,但AQP-5表达并未发生改变;且虽秋燥和西北燥邪微观致病机制不尽相同,但健康机体对此具有习服能力。正虚是燥邪致病的内因,本研究以维持肺泡表面气液平衡且具固有免疫功能的SP-D为正气卫外的标志物,拟运用iTRAQ和生物信息学技术分析正常组、秋燥组、西北燥邪组、SP-D KO秋燥组、SP-D KO西北燥邪组大鼠肺、降结肠的差异表达蛋白,在比较秋燥与西北燥微观致病机制中寻找更有价值的线索,为阐发基于燥邪致病的肺与大肠相表里及外燥证分子机制提供依据,也为基于证实质探索干旱半干旱区中医药防治外燥证做准备。
英文摘要
Northwest Dryness Syndrome(NDS) is the combine TCM syndrome causing by northwest dryness evil(climatic factors of arid and semi-arid area),NDS suffering is the risk and aggravating factor of the pathogenesis of many kinds of special high incidence diseases or sub-health in northwest China,study of dryness evil pathogenicity essence will help scientific prevention and treatment of dryness syndrome.. Our former research have establish and verify dryness laboratory simulation program that made it possible to compare the microcosmic pathogenesis of autumn dryness evil(ADE) and northwest dryness evil(NDE),we have verified that dryness evil induced SP-D enhanced expression in lungs and airways,and hyperactive immune function of cells in the body, but the expression of AQP-5 was not changed.And although the microcosmic pathogenesis of ADE and NDE is not the same, the healthy organism has the ability to adapt to it.. Zhengqi deficiency is the internal cause of the disease caused by external pathogenic factors.In this study, SP-D, which maintains the gas-liquid balance on the surface of alveoli and has inherent immune function, is used as a marker of the external defense function of zhengqi. ITRAQ and bioinformatics will be used to analyze the differential expression of proteins in the lung and descending colon of rats between the normal group, ADE group, NDE group and SP-D ko ADE group, and SP-D ko NDE group, so as to find and verify more valuable clues during comparing the micropathogenesis of autumn dryness evil and northwest northwest dryness group.This study provides a basis for the elucidation of "lung & large intestine interior-exterior relationship" theory and the molecular mechanism of external dryness syndrome based on the pathogenic factors of dryness, and also makes preparations for the exploration of TCM prevention and treatment of external dryness syndrome in arid and semi-arid areas based on the essence of the syndrome.
燥气主令于秋亦盛于干旱之域,燥邪有秋燥与方域燥之别。项目组前期研究证实秋燥和方域燥致病机制相异。本研究以人工模拟的秋燥和方域燥干预健康大鼠和SP-D基因敲除大鼠,采用蛋白质组学技术筛选正常对照组、秋燥组、方域燥组、SP-D ko秋燥组、SP-D ko方域燥组大鼠肺、降结肠中的差异表达蛋白,基于生信分析和靶标验证,从正虚(SP-D 基因敲除)和邪盛两个角度探索燥邪致病及“肺和大肠相表里”的分子学基础。.差异表达蛋白层次聚类分析结果显示,各燥邪干预组与正常对照组组间样本呈差异表达蛋白分组模式。验证靶标后发现秋燥不影响肺SP-D表达(P>0.05),秋燥或SP-D基因敲除后未见肺SP-A、IFIT3、Gstm1、LIAS、NF-κB异常表达(P>0.05),但SP-D基因敲除可致肺SP-A上调(P<0.05),秋燥和SP-D基因敲除的交互效应不影响肺SP-A表达(P>0.05),SP-A或可代偿SP-D的不足从而发挥保护性作用。.方域燥可致肺SP-A(上调)、SP-D(下调)、TRAF3(上调)、XPR1(下调)、MU5AC(下调)表达发生变化(P<0.05),pERK/ERK升高(P<0.05),但不引起肺CAP2、NF-κB、pSHP-1/SHP-1、SIRPα异常变化(P>0.05)。SP-D基因敲除与方域燥的交互效应影响肺SP-A、TRAF3、XPR1、pERK/ERK和MU5AC表达(P<0.05)。方域燥可致结肠SP-A、MU5AC表达上调(P<0.05),但仅后者受基因敲除和方域燥交互效应的影响(P>0.05)。肺SP-D、MU5AC、XPR1异常表达是方域燥伤肺的分子学基础,肺SP-A、TRAF3的上调可能与机体适应干旱环境有关,可从肺泡气液表面平衡、炎性反应调节及细胞磷酸盐环境稳态等方面探索“燥邪伤肺”及机体习服干旱环境的机制。SP-A可能是燥邪致病中肺和大肠相表里的分子学基础,肺SP-D不足可以是正虚无以御燥的分子学基础,或可用于判断机体干旱环境适应力。基于生物信息学分析,两种燥邪致病差异性可能与肺Casp8、Mrps5、C3,结肠Rnf149,Plbd2,Rgs1等有关,可优选细胞凋亡、补体和凝血级联反应、溶酶体通路进行探索;而RT1-Db1是探索肺和大肠相表里机制的唯一靶标,可关注RT1-Db1与Nid2、Rgs1、Zap70的互作开展研究。
西北燥证型亚健康大鼠模型的建立与评价研究
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批准号:--
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项目类别:地区科学基金项目
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资助金额:35万元
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批准年份:2022
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负责人:史红
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依托单位:
基于干旱环境影响大鼠慢性支气管炎病变过程的西北燥证证候机制研究
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批准号:81560742
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项目类别:地区科学基金项目
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资助金额:37.0万元
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批准年份:2015
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负责人:史红
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依托单位:
国内基金
海外基金