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清燥方基于 PI3K/Akt/HIF-1/VEGF 信号通路减轻干燥综合征颌下腺炎性微环境。

Qing Zao Fang (QZF) Alleviates the Inflammatory Microenvironment of the Submandibular Gland in Sjögren's Syndrome Based on the PI3K/Akt/HIF-1/VEGF Signaling Pathway.

机构信息

First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.

National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 300381, China.

出版信息

Dis Markers. 2022 Jan 31;2022:6153459. doi: 10.1155/2022/6153459. eCollection 2022.

Abstract

Sjögren's syndrome (SS) which could lead to a disorder of our immune system is a chronic autoimmune disease characterized by invading exocrine glands such as salivary glands and lacrimal glands and other exocrine glands. Its common symptom is dry mouth and dry eyes, often accompanied by a large number of lymphocyte infiltrations and can involve other organs to cause complex clinical manifestations. In this study, we aimed at investigating the effect of QZF in SS, identifying the molecular mechanism in modulating autoimmune response, and determining the important roles of these factors' function as a modulator in the pathogenesis of SS. The NOD mice were utilized to establish the rats' model of Sjögren's syndrome. After 10 weeks' hydroxychloroquine and QZF in different dose interference, submandibular gland tissue was collected. The therapeutic effect of QZF on SS rats was identified, and the results suggest the comparable potential to hydroxychloroquine. In submandibular gland tissue, interleukin- (IL-) 17 was significantly lower in high-dose QZF than that in SS rats and the focal lymphocytes were highly attenuated. Moreover, we found that PI3K/Akt signals were activated and the downstream HIF-1/VEGF signals were enhanced in SS rats whose protein expression could be inhibited by QZF treatment. In addition, QZF could modulate autophagy in submandibular gland tissue and then inhibit the inflammation response and therefore facilitate the tissue repair.

摘要

干燥综合征(SS)可导致免疫系统紊乱,是一种以侵犯外分泌腺,如唾液腺和泪腺等,及其他外分泌腺为特征的慢性自身免疫性疾病。其常见症状为口干、眼干,常伴有大量淋巴细胞浸润,并可累及其他器官,引起复杂的临床表现。在这项研究中,我们旨在研究 QZF 在 SS 中的作用,确定调节自身免疫反应的分子机制,并确定这些因子作为 SS 发病机制调节剂的功能的重要作用。我们利用 NOD 小鼠建立干燥综合征大鼠模型。经过 10 周的羟氯喹和 QZF 不同剂量的干预后,收集颌下腺组织。鉴定 QZF 对 SS 大鼠的治疗效果,结果表明其具有与羟氯喹相当的潜力。在颌下腺组织中,高剂量 QZF 组的白细胞介素-17(IL-17)明显低于 SS 大鼠,局灶性淋巴细胞高度减弱。此外,我们发现 SS 大鼠的 PI3K/Akt 信号被激活,下游的 HIF-1/VEGF 信号增强,而 QZF 治疗可抑制其蛋白表达。此外,QZF 可调节颌下腺组织中的自噬,从而抑制炎症反应,促进组织修复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2da/8820932/964155ba6cb7/DM2022-6153459.001.jpg

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