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DNA受体Toll样受体9信号通路通过抑制炎症反应和氧化应激在新生儿急性肺损伤中发挥主要免疫调节作用。

DNA Receptor Toll-Like Receptor 9 Signaling Pathway Plays a Major Immunomodulatory Role in Neonatal Acute Lung Injury by Inhibiting Inflammatory Response and Oxidative Stress.

作者信息

Liu Weiyun, Zheng Yunping, Liu Liyan

机构信息

Department of Neonatology, Xinyu Peoples Hospital, Xinyu, Jiangxi Province, China.

Department of Electrophysiological Diagnosis, Xinyu Peoples Hospital, Xinyu, Jiangxi Province, China.

出版信息

Cell Biochem Biophys. 2025 Mar 7. doi: 10.1007/s12013-025-01704-7.

Abstract

To investigate the clinical efficacy of neonatal acute lung injury (NALI) and the mechanistic role of the DNA sensor Toll-like receptor 9 (TLR9) signaling pathway in treatment, Methods: This study enrolled 76 cases of NALI, randomly divided into 38 cases in the experimental group (intravenous injection of human immunoglobulin on the basis of nasal continuous positive airway pressure ventilation treatment) and 38 cases in the control group (nasal continuous positive airway pressure ventilation treatment). The pulmonary function parameters (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC), TLR9 signaling pathway-related proteins and mRNA levels (TLR9, MyD88, p38), inflammatory factors (C-reactive protein (CRP), interleukin (IL)-1β, tumor necrosis factor (TNF)-α), and immune function indicators (immunoglobulin (Ig)A, IgG, IgM) were compared between the two groups. Pearson correlation analysis was conducted to examine the relationship between TLR9 signaling pathway protein expression and immune function indicators.After treatment, the pulmonary function parameters FVC, FEV1, and FEV1/FVC in neonates in the experimental group were considerably higher than those in the control group (P < 0.05). The serum levels of inflammatory factors CRP, IL-1β, and TNF-α in the experimental group of neonates following treatment were significantly lower than those in the control group (P < 0.05). After treatment, the levels of immune function indicators IgA, IgG, and IgM in neonates in the experimental group were considerably lower than those in the control group (P < 0.05). The protein expression levels of TLR9 showed a highly significant positive correlation with neonatal immune function indicators IgA, IgG, and IgM levels (P < 0.001). MyD88 protein expression exhibited a significant positive correlation with neonatal immune function indicators IgA, IgG, and IgM levels (P < 0.05). p38 protein expression demonstrated a significant positive correlation with neonatal immune function indicators IgA, IgG, and IgM levels (P < 0.05). In summary, the potential role of DNA receptor TLR9 signaling pathway-related proteins in the treatment of neonates with lung injury has been explored. The changes in the expression levels of TLR9/MyD88/p38 are associated with the production or regulation of immunoglobulins, and this association shows a certain correlation with the clinical efficacy in neonates with lung injury.

摘要

为探讨新生儿急性肺损伤(NALI)的临床疗效以及DNA传感器Toll样受体9(TLR9)信号通路在治疗中的作用机制,方法:本研究纳入76例NALI患儿,随机分为实验组38例(在经鼻持续气道正压通气治疗基础上静脉注射人免疫球蛋白)和对照组38例(经鼻持续气道正压通气治疗)。比较两组的肺功能参数(用力肺活量(FVC)、第1秒用力呼气量(FEV1)和FEV1/FVC)、TLR9信号通路相关蛋白和mRNA水平(TLR9、MyD88、p38)、炎症因子(C反应蛋白(CRP)、白细胞介素(IL)-1β、肿瘤坏死因子(TNF)-α)以及免疫功能指标(免疫球蛋白(Ig)A、IgG、IgM)。采用Pearson相关分析检测TLR9信号通路蛋白表达与免疫功能指标之间的关系。治疗后,实验组新生儿的肺功能参数FVC、FEV1和FEV1/FVC显著高于对照组(P<0.05)。治疗后实验组新生儿血清炎症因子CRP、IL-1β和TNF-α水平显著低于对照组(P<0.05)。治疗后,实验组新生儿免疫功能指标IgA、IgG和IgM水平显著低于对照组(P<0.05)。TLR9蛋白表达水平与新生儿免疫功能指标IgA、IgG和IgM水平呈高度显著正相关(P<0.001)。MyD88蛋白表达与新生儿免疫功能指标IgA、IgG和IgM水平呈显著正相关(P<0.05)。p38蛋白表达与新生儿免疫功能指标IgA、IgG和IgM水平呈显著正相关(P<0.05)。综上所述,探讨了DNA受体TLR9信号通路相关蛋白在新生儿肺损伤治疗中的潜在作用。TLR9/MyD88/p38表达水平的变化与免疫球蛋白的产生或调节有关,且这种关联与新生儿肺损伤的临床疗效呈现一定相关性。

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