首页|大蒜素治疗大肠埃希菌诱导的急性膀胱炎的分子机制研究

大蒜素治疗大肠埃希菌诱导的急性膀胱炎的分子机制研究

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目的 探讨大蒜素在治疗大肠埃希菌诱导的急性膀胱炎中的作用及潜在的机作用机制。方法 研究首先通过构建大鼠急性膀胱炎模型,并进行大蒜素治疗,取大鼠膀胱组织进行HE染色观察组织结构改变以确定大蒜素的治疗效果;接着对不同分组的大鼠膀胱组织进行转录组测序并结合GEO数据分析大蒜素可能作用的下游靶点,通过GO与KEGG及蛋白互作(PPI)等分析筛选潜在分子靶点,进而在大鼠膀胱组织切片中进行免疫组化的实验验证。结果 大鼠膀胱组织切片HE染色结果显示大蒜素可缓解急性膀胱炎的组织结构紊乱及免疫细胞浸润程度,存在显著疗效;大鼠膀胱组织的转录组测序结果显示大蒜素可显著抑制115个在急性膀胱炎中上调的蛋白及诱导24个下调的蛋白,结合GEO中C57小鼠膀胱炎症的测序结果后,筛选出37个共同上调的蛋白及1个下调的蛋白,功能富集分析显示,这些基因主要集中在免疫相关的通路上,包括免疫反应调控、T细胞受体信号通路、Th17细胞分化、Th1和Th2细胞分化、细胞因子-免疫因子受体相互作用等。通过蛋白互作分析研究进一步筛选出CD74,CD96,ICOS,PTPN22,PDCD1,CXCR6等免疫细胞相关因子,结合其在大鼠中的测序丰度,最终筛选出差异最显著的CD74;实验结果进一步证明,大蒜素可抑制尿路上皮CD74表达进而抑制巨噬细胞在大肠杆菌诱导的急性膀胱炎中的浸润分布,缓解炎症反应。结论 本研究发现大蒜素可治疗大肠杆菌诱导的急性膀胱炎症,为研究大蒜素等天然抗菌单体治疗急性膀胱炎提供了新的方向与策略。
Molecular Mechanism of Allicin in the Treatment of Acute Cystitis Inflammation Induced by Escherichia Coli
OBJECTIVE To delve into the therapeutic role of allicin in addressing Escherichia coli-triggered acute cystitis and the potential underlying mechanisms.METHODS An acute cystitis model was established in rats,and treated with allicin administration.The pathological changes of rat bladder tissues were observed by HE staining to observe allicin's therapeutic effect.The bladder tissue transcriptome sequencing was conducted across distinct rat groups.In tandem with GEO data analysis,downstream targets influenced by allicin were discerned.Potential molecular targets were screened through GO,KEGGenrichment analysis,and protein-protein interaction analysis(PPI).The experimental ofimmunohistochemistry on rat bladder tissue sections was valiated.RESULTS The results depicted allicin diminished structural disarray within rat bladder tissue sections and reduced immune cell infiltration,showing substantial therapeutic efficacy against acute cystitis.Transcriptome sequencing of rat bladder tissues revealed allicin's significant suppression of 115 upregulated proteins and induction of 24 downregulated proteins in acute cystitis,amalgamated with C57 mouse bladder inflammation sequencing data from GEO,37 commonly upregulated proteins and 1 downregulated protein were identified.Functional enrichment analysis showed that the dominance of immune-related pathways,encompassed immune response regulation,T cell receptor signaling,Th 17 cell differentiation,Th l and Th2 cell differentiation,cytokine-immune factor receptor interaction and more.Further dissection via PPI identified immune cell-associated factors such as CD74,CD96,ICOS,PTPN22,PDCD1,and CXCR6.Combined with their sequencing abundance of in rats,CD74 with the most significant difference was finally selected.Empirical findings furthervalidatedthat allicin curbed urinary epithelial CD74 expression,mitigated macrophage infiltration dispersion in E.coli-induced acute cystitis,ameliorated inflammatory response.CONCLUSION This study unearths allicin's potential in E.coli-induced acute cystitis treatment,providing a method for exploring the therapeutic potential of natural antimicrobial monomers like allicin in managing acute cystitis.

allicinescherichia coliacute cystitistranscriptome sequencing

张玉艳、陈倩梅、刘银欢、龙惠

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广州市皮肤病医院,广东广州 510095

大蒜素 大肠埃希菌 急性膀胱炎 转录组测序

广州市科技计划广东省医院药学研究基金澳美基金广东省中医药局项目

2022010100482023A2220221313

2024

今日药学
广东省药学会 中国药学会

今日药学

影响因子:0.413
ISSN:1674-229X
年,卷(期):2024.34(1)
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