自噬抑制急性肾损伤诱导急性肺损伤的分子机制OA北大核心CSTPCD

Objective This study aimed to explore the regulatory role of autophagy in acute kidney injury(AKI)-induced acute liver injury(ALI).Methods Forty-eight male Sprague-Dawley rats were randomly divided into four groups:sham operation group,IRI group,3-MA group and RA group.Except for the sham operation group,a rat model of AKI induced by IRI was established in all groups.The AKI model was established by removing the right kidney,separating the left renal artery,and clamping the left renal artery,followed by reper-fusion for 12,24,48,or 72 h.The 3-MA and RA groups were intraperitoneally injected with 3-MA(15 mg/kg,1 mL)or RA(2 mg/kg,1 mL)12 h before and after IRI treatment.The structure and function of the rat lung and kidney tissues were evaluated,and the expression levels of autophagy-related proteins,oxidative stress,and apoptosis were measured.Results Renal IRI led to ALI after AKI,and the levels of blood urea nitrogen,creatinine,tumor necrosis factor-α,and interleukin-1βwere all significantly increased.In addition,compared to the IRI group,the expression levels of P62 and caspase-3 significantly decreased in the RA group,whereas the expression levels of LC3-Ⅱ/LC3-Ⅰ,Beclin-1,Bcl-2,and ULK1 increased.Autophagy reduced pathological damage to kidney and lung tissues by inhibiting inflammation and oxidative stress and effectively ameliorated AKI-induced ALI.Conclusion Autophagy plays an important role in the regulation of ALI induced by AKI and can be used as a new target for AKI treatment and to reduce complication-related mortality.