Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China;
Department of Nephrology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
Allergol Immunopathol (Madr). 2022 Nov 1;50(6):187-194. doi: 10.15586/aei.v50i6.733. eCollection 2022.
Sepsis-induced acute kidney injury is a general critical complication having high relevance to kidney inflammation. In spite of advances in clinical and critical care, the specific and effective therapies for acute kidney injury are still insufficient. The present study aimed to investigate the protective effect of Iroquois homeobox genes () on sepsis-induced kidney dysfunction in mice.
In order to gain insight into sepsis-related actions in acute kidney injury, the cecal puncture-induced kidney injury animal model was established. The hematoxylin and eosin staining was used to measure the pathology of kidney tissues. The kidney function-related biomarkers, including neutrophil gelatinase-associated lipocalin, creatinine, kidney injury molecule-1, blood urea nitrogen, and inflammatory cytokines, which included tumor necrosis factor α, interleukin 1β (IL-1β), IL-6, and monocyte chemotactic protein 1, were detected by automated biochemical analyzer or their corresponding test kits. The protein expression was measured using Western blot analysis, and the apoptotic rate of kidney tissue was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling assay.
The present study revealed the protective ability of in sepsis-induced acute kidney injury. This study also determined the potential mechanism of on sepsis-induced inflammatory response and cell apoptosis. Finally, it highlighted that exerted a protective influence on CLP-induced acute kidney injury by suppressing the activation of chemokine (C-X-C motif) ligand 14 (CXCL14).
To conclude, the results suggest that overexpression of could promote survival rate and suppress the CLP-induced apoptosis, inflammatory response, and kidney dysfunction through the activation of CXCL14. and CXCL14 are essential to elucidate the mechanism of acute kidney injury. These findings may help to identify the promising targets for clinical sepsis therapy.
脓毒症诱导的急性肾损伤是一种与肾脏炎症密切相关的常见危重并发症。尽管临床和重症监护方面取得了进展，但针对急性肾损伤的特异性和有效治疗方法仍然不足。本研究旨在探讨 Iroquois 同源盒基因 () 对小鼠脓毒症诱导的肾功能障碍的保护作用。
为了深入了解脓毒症相关的急性肾损伤作用，建立了盲肠穿刺诱导的肾损伤动物模型。苏木精-伊红染色用于测量肾组织的病理变化。采用自动生化分析仪或相应试剂盒检测中性粒细胞明胶酶相关脂质运载蛋白、肌酐、肾损伤分子-1、血尿素氮和炎症细胞因子（肿瘤坏死因子-α、白细胞介素 1β [IL-1β]、白细胞介素 6 和单核细胞趋化蛋白 1）等肾功能相关生物标志物。采用 Western blot 分析检测蛋白表达，采用末端脱氧核苷酸转移酶 dUTP 缺口末端标记法检测肾组织细胞凋亡率。
本研究揭示了在脓毒症诱导的急性肾损伤中 具有保护作用。本研究还确定了 对脓毒症诱导的炎症反应和细胞凋亡的潜在作用机制。最后，强调 通过抑制趋化因子（C-X-C 基序）配体 14 (CXCL14) 的激活，对 CLP 诱导的急性肾损伤发挥保护作用。
综上所述，结果表明，过表达 可通过激活 CXCL14 提高存活率并抑制 CLP 诱导的凋亡、炎症反应和肾功能障碍。和 CXCL14 是阐明急性肾损伤机制的关键。这些发现可能有助于确定临床脓毒症治疗的有前途的靶点。
