Hypobaric Hypoxia Aggravates Renal Injury by Inducing the Formation of Neutrophil Extracellular Traps through the NF-kappa B Signaling Pathway

作者全名："Wei, Jun-yu; Hu, Miao-yue; Chen, Xiu-qi; Wei, Jin-shuang; Chen, Jie; Qin, Xuan-kai; Lei, Feng-ying; Zou, Jia-sen; Zhu, Shi-qun; Qin, Yuan-han"

作者地址："[Wei, Jun-yu; Hu, Miao-yue; Chen, Xiu-qi; Wei, Jin-shuang; Chen, Jie; Qin, Xuan-kai; Lei, Feng-ying; Qin, Yuan-han] Guangxi Med Univ, Affiliated Hosp 1, Dept Pediat, Nanning 530021, Peoples R China; [Zou, Jia-sen] Chongqing Med Univ, Childrens Hosp, Chongqing 400015, Peoples R China; [Zhu, Shi-qun] Shenzhen Childrens Hosp, Shenzhen 518034, Peoples R China"

通信作者："Qin, YH (通讯作者)，Guangxi Med Univ, Affiliated Hosp 1, Dept Pediat, Nanning 530021, Peoples R China."

来源：CURRENT MEDICAL SCIENCE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001000323100001

JCR分区：Q3

影响因子：2

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：hypobaric hypoxia; neutrophil extracellular traps; hypoxia; kidney injury; NF-kappa B; apoptosis

摘要："Objective: The hypersensitivity of the kidney makes it susceptible to hypoxia injury. The involvement of neutrophil extracellular traps (NETs) in renal injury resulting from hypobaric hypoxia (HH) has not been reported. In this study, we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism. Methods: A total of 24 SD male rats were divided into three groups (n=8 each): normal control group, hypoxia group and hypoxia+pyrrolidine dithiocarbamate (PDTC) group. Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters (oxygen partial pressure about 6.9 kPa) for 7 days. PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days. Pathological changes of the rat renal tissues were observed under a light microscope; the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cell-free DNA (cf-DNA) and reactive oxygen species (ROS) were measured; the expression levels of myeloperoxidase (MPO), citrullinated histone H3 (cit-H3), B-cell lymphoma 2 (Bcl-2), Bax, nuclear factor kappa B (NF-?B) p65 and phospho-NF-?B p65 (p-NF-?B p65) in rat renal tissues were detected by qRT-qPCR and Western blotting; the localization of NF-?B p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining. Results: After hypoxia, the expression of NF-?B protein in renal tissues was significantly increased, the levels of SCr, BUN, cf-DNA and ROS in serum were significantly increased, the formation of NETs in renal tissues was significantly increased, and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues. When PDTC was used to inhibit NF-?B activation, NETs formation in renal tissue was significantly decreased, the expression level of Bcl-2 in renal tissues was significantly increased, the expression level of Bax was significantly decreased, and renal injury was significantly alleviated. Conclusion: HH induces the formation of NETs through the NF-?B signaling pathway, and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression."

基金机构：Guangxi Medical High-level Key Talents/139 [G201901010]; Natural Science Foundation of Guangxi Province

基金资助正文：This work was supported by grants from Guangxi Medical High-level Key Talents/139/(No. G201901010) and Natural Science Foundation of Guangxi Province (No. GXNSFDA198008).