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脊髓损伤大鼠直肠肠道相关淋巴组织内生物标志物表达水平的变化。

Biomarker expression level changes within rectal gut-associated lymphoid tissues in spinal cord-injured rats.

作者信息

Zhou Yun, Hubscher Charles H

机构信息

Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY, United States.

Kentucky Spinal Cord Injury Research Center, Louisville, KY, United States.

出版信息

Immunohorizons. 2025 Feb 18;9(4). doi: 10.1093/immhor/vlaf002.

Abstract

Neurogenic bowel dysfunction (NBD) is common after spinal cord injury (SCI). Gut-associated lymphoid tissue (GALT), an organized structure within the mucosal immune system, is important for the maintenance of gut homeostasis and body health and serves as the first line barrier/defense against diet antigens, commensal microbiota, pathogens, and toxins in mucosal areas. The current study examined gene expression levels along six segments of anorectal tissue using real-time polymerase chain reaction (RT-PCR) in uninjured rats (28-day sham surgical controls) and at both 28- and 42-days post-T9 contusion injury. Consistent with our previous report of functional regional differences in the ano-rectum, we demonstrate the existence of GALTs located primarily within the segment at 3-4.5 cm from the rectal dentate line (termed rectal GALTs-rGALTs) in shams with upregulated gene expression levels of multiple biomarkers, including B cell and T cell-related genes, major histocompatibility complex (MHC) class II molecules, and germinal center (GC)-related genes, which was further confirmed by histologic examination. In the same rectal tissue segment following T9 SCI, inflammation-related genes were upregulated at 28 days post-injury (DPI) indicating that microbial infection and inflammation of rGALTs modified structure and function of rGALTs, while at 42 DPI rGALTs exhibited resolution of inflammation and impaired structure/function for extrafollicular B cell responses. Taken together, our data suggest that rGALTs exists in rat rectum for homeostasis of gut microbiota/barrier. SCI induces microbial infection and inflammation in rectal tissues containing rGALTs, which could contribute to development of SCI-related gut microbiome dysbiosis, NBD, and systemic diseases.

摘要

神经源性肠道功能障碍(NBD)在脊髓损伤(SCI)后很常见。肠道相关淋巴组织(GALT)是黏膜免疫系统中的一种组织结构,对维持肠道内环境稳定和身体健康很重要,并且作为黏膜区域抵御饮食抗原、共生微生物群、病原体和毒素的第一道屏障/防线。本研究使用实时聚合酶链反应(RT-PCR)检测了未受伤大鼠(28天假手术对照组)以及T9挫伤损伤后28天和42天的肛门直肠组织六个节段的基因表达水平。与我们之前关于肛门直肠功能区域差异的报告一致,我们证明在假手术组中,主要位于距直肠齿状线3 - 4.5厘米节段内的GALT(称为直肠GALT - rGALT)存在,多种生物标志物的基因表达水平上调,包括B细胞和T细胞相关基因、主要组织相容性复合体(MHC)II类分子以及生发中心(GC)相关基因,组织学检查进一步证实了这一点。在T9脊髓损伤后的同一直肠组织节段中,损伤后28天(DPI)炎症相关基因上调,表明rGALT的微生物感染和炎症改变了rGALT的结构和功能,而在42 DPI时,rGALT表现出炎症消退以及滤泡外B细胞反应的结构/功能受损。综上所述,我们的数据表明rGALT存在于大鼠直肠中以维持肠道微生物群/屏障的内环境稳定。脊髓损伤会在含有rGALT的直肠组织中引发微生物感染和炎症,这可能导致脊髓损伤相关的肠道微生物群失调、神经源性肠道功能障碍和全身性疾病的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7d4/11884801/1c4be47124ca/vlaf002f1.jpg

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