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Background:Acute kidney injury (AKI) is the most common and life-threatening systemic complication ofrhabdomyolysis.Inflammation plays an important role in the development of rhabdomyolysis-induced AKI.This study aimed to investigate the kidney model of AKI caused by rhabdomyolysis to verify the role ofmacrophage Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway.Methods:C57BL/6 mice were injected with a 50％ glycerin solution at bilateral back limbs to induce rhabdomyolysis,and CLI-095 or pyrrolidine dithiocarbamate (PDTC) was intraperitoneally injected at 0.5 h before molding.Serum creatinine levels,creatine kinase,the expression of tumor necrosis factor (TNF)-c,interleukin (IL)-1β and I L-6,and hematoxylin and eosin stainings of kidney tissues were tested.The infiltration of macrophage,mRNA levels,and protein expression of TLR4 and NF-κB were investigated by immunofluorescence double-staining techniques,reverse transcriptase-quantitative polymerase chain reaction,and West blotting,respectively.In vitro,macrophage RAW264.7 was stimulated by ferrous myoglobin;the cytokines,TLR4 and NF-κB expressions were also detected.Results:In an in vivo study,using CLI-095 or PDTC to block TLR4/NF-κB,functional and histologic results showed that the inhibition of TLR4 or NF-κB alleviated glycerol-induced renal damages (P ＜ 0.0 1).CLI-095 or PDTC administration suppressed proinflammatory cytokine (TNF-c,IL-6,and IL-1 β) production and macrophage infiltration into the kidney (P ＜ 0.01).Moreover,in an in vitro study,CLI-095 or PDTC suppressed myoglobin-induced expression ofTLR4,NF-κB,and proinflammatory cytokine levels in macrophage RAW264.7 cells (P ＜ 0.01).Conclusion:The pharmacological inhibition of TLR4/NF-κB exhibited protective effects on rhabdomyolysis-induced AKI by the regulation of proinflammatory cytokine production and macrophage infiltration.