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TLR4/NF-κB 通路在大鼠急性低压缺氧性小肠黏膜损伤中的作用。

Role of TLR4/NF-κB pathway in the damage of acute hypobaric hypoxia to small intestinal mucosa in rats.

机构信息

Department of Gastroenterology, Lianyungang Hospital of Traditional Chinese Medicine, Lianyungang City, Jiangsu Province, China.

出版信息

Gen Physiol Biophys. 2021 Jan;40(1):79-88. doi: 10.4149/gpb_2020042.

Abstract

The purpose of this study was to investigate the effect of acute hypobaric hypoxia (HH) exposure on small intestinal mucosa in rats and its underling mechanism. The pathological changes of rat small intestine mucosa were detected by HE staining. The expressions of TLR4 and NF-κB in the small intestine were detected by immunohistochemistry (IHC). The levels of Zonulin, TNF-α, IL-1β, and IL-6 in the serum were detected by ELISA. The proportion of natural killer (NK) cells and dendritic cell population in the small intestine was analyzed by flow cytometry. The mRNA and protein levels of TLR4, NF-κB, occludin, HIF-1α, and iNOS were detected by RT-qPCR and Western blot, respectively. Compared with the Control group, the HH groups had different degrees of injury in intestinal mucosa. Meanwhile, in the HH groups, it was also found the increased levels of Zonulin, TNF-α, IL-1β and IL-6 in the serum, the increased CD4+/CD8+T cells ratio and small intestine NK cells population, the increased mRNA and protein expression levels of small intestine TLR4, NF-κB, HIF-1α and iNOS, and the decreased mRNA and protein expression levels of occludin. Acute HH may damage the intestinal mucosa of rats by inducing TLR4/NF-κB pathway overexpression.

摘要

本研究旨在探讨急性低压缺氧(HH)暴露对大鼠小肠黏膜的影响及其潜在机制。通过 HE 染色检测大鼠小肠黏膜的病理变化。采用免疫组织化学(IHC)检测 TLR4 和 NF-κB 在小肠中的表达。通过 ELISA 检测血清中 Zonulin、TNF-α、IL-1β 和 IL-6 的水平。通过流式细胞术分析小肠中自然杀伤(NK)细胞和树突状细胞群体的比例。通过 RT-qPCR 和 Western blot 分别检测 TLR4、NF-κB、occludin、HIF-1α 和 iNOS 的 mRNA 和蛋白水平。与对照组相比,HH 组的肠黏膜有不同程度的损伤。同时,在 HH 组中,还发现血清中 Zonulin、TNF-α、IL-1β 和 IL-6 的水平升高,小肠 CD4+/CD8+T 细胞比值和 NK 细胞群体增加,小肠 TLR4、NF-κB、HIF-1α 和 iNOS 的 mRNA 和蛋白表达水平升高,occludin 的 mRNA 和蛋白表达水平降低。急性 HH 可能通过诱导 TLR4/NF-κB 通路过度表达来损伤大鼠的肠黏膜。

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