Department of Intensive care unit, The First Affiliated Hospital of Gannan Medical University, 128 Jinling Avenue, Zhanggong District, Ganzhou, Jiangxi Province, 341000, China.
Department of Pediatric Surgery, The First Affiliated Hospital of Gannan Medical University, 128 Jinling Avenue, Zhanggong District, Ganzhou, Jiangxi Province, 341000, China.
J Bioenerg Biomembr. 2023 Oct;55(5):353-363. doi: 10.1007/s10863-023-09972-9. Epub 2023 Aug 22.
Septic acute kidney injury (AKI) contributes to the mortality and morbidity of sepsis patients. Toll-like Receptor 4 (TLR4) has prominent roles in septic AKI. This study investigated the functions of TLR4 in septic AKI. A septic AKI mouse model was established by cecal ligation and puncture surgery. Mouse kidney function and kidney tissue lesion were examined using corresponding kits and H&E staining. The in vitro cell model of septic AKI was established by lipopolysaccharide induction. Cell viability, inflammatory factor (TNF-α, IL-6, IL-4, IL-1β, IL-18) levels, pyroptotic cell number changes, lactate dehydrogenase (LDH) activity, myeloperoxidase (MOP) concentration, and levels of pyroptosis-associated protein and MyD88, TRIF and p38 MAPK phosphorylation were determined by MTT, ELISA, FAM-FLICA Caspase-1 Detection kit, other corresponding kits, and Western blot. TLR4 was highly expressed in septic AKI mouse kidney tissues and human septic AKI cells. TLR4 knockdown alleviated kidney injury, increased cell viability, and reduced LDH activity and MPO concentration. TLR4 knockdown reduced cell pyroptosis by repressing p38 MAPK phosphorylation through MyD88/TRIF, suppressed pro-inflammatory factor (TNF-α, IL-6, IL-4, IL-1β, IL-18) levels, promoted anti-inflammatory factor (IL-4) level, and reduced inflammatory response, thus playing a protective role in septic AKI. Briefly, TLR4 promoted the inflammatory response in septic AKI by promoting p38 MAPK phosphorylation through MyD88/TRIF.
脓毒症急性肾损伤（AKI）导致脓毒症患者的死亡率和发病率升高。Toll 样受体 4（TLR4）在脓毒症 AKI 中具有重要作用。本研究探讨了 TLR4 在脓毒症 AKI 中的作用。通过盲肠结扎穿孔术建立脓毒症 AKI 小鼠模型。使用相应试剂盒和 H&E 染色检测小鼠肾功能和肾组织损伤。通过脂多糖诱导建立脓毒症 AKI 的体外细胞模型。通过 MTT、ELISA、FAM-FLICA Caspase-1 Detection kit、其他相应试剂盒和 Western blot 测定细胞活力、炎症因子（TNF-α、IL-6、IL-4、IL-1β、IL-18）水平、细胞焦亡数变化、乳酸脱氢酶（LDH）活性、髓过氧化物酶（MPO）浓度、细胞焦亡相关蛋白和 MyD88、TRIF 和 p38 MAPK 磷酸化水平。TLR4 在脓毒症 AKI 小鼠肾脏组织和人脓毒症 AKI 细胞中高表达。TLR4 敲低减轻了肾损伤，增加了细胞活力，降低了 LDH 活性和 MPO 浓度。TLR4 敲低通过抑制 MyD88/TRIF 抑制 p38 MAPK 磷酸化来减少细胞焦亡，抑制促炎因子（TNF-α、IL-6、IL-4、IL-1β、IL-18）水平，促进抗炎因子（IL-4）水平，减轻炎症反应，从而在脓毒症 AKI 中发挥保护作用。总之，TLR4 通过 MyD88/TRIF 促进 p38 MAPK 磷酸化，在脓毒症 AKI 中促进炎症反应。
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