Hydrogen sulfide attenuates urosepsis-induced acute kidney injury by blocking TLR4/MyD88/PI3K signaling pathway / 中国病理生理杂志

ABSTRACT

AIM:To explore the effect of hydrogen sulfide (H2S) on urosepsis-induced acute kidney injury.METHODS:New Zealand white rabbits were randomly divided into control group, sham group, model (sepsis) group, Na HS treatment (Na HS) group, and Na HS combined with TAK-242 (a TLR4 inhibitor) treatment (Na HS+TAK-242) group.After treatment for 72 h, HE staining was used to measure the histopathological changes of rabbit kidney.The levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected by automatic biochemical analyzer.The serum levels of neutrophil gelatinase-associated lipocalin (NGAL) , kidney injury molecule 1 (KIM-1) , procalcitonin (PCT) , interleukin-1β (IL-1β) , interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA.The TLR4/MyD88/PI3K signaling pathway-related proteins in the kidney were determined by Western blot.RESULTS:Compared with control group, obvious damage was observed in the kidneys of septic rabbits, but the kidneys were markedly improved by treatment with Na HS.The levels of BUN, SCr, NGAL, KIM-1, PCT, IL-1β, IL-6 and TNF-αin the septic rabbits were higher than those in control group, and decreased significantly in Na HS group and Na HS+TAK-242 group.The protein levels of TLR4, MyD88, p-PI3K and p-Akt in septic rabbit kidneys were higher than those in control group.However, Na HS or Na HS+TAK-242 inhibited the activation of TLR4/MyD88/PI3K signaling pathway in the kidneys of septic rabbits.CONCLUSION:H2S play a protective effect on the rabbits with urosepsis-induced acute kidney injury by blocking TLR4/MyD88/PI3K signaling pathway to inhibit inflammatory response.