Sevoflurane Attenuates Hepatic Ischemia-reperfusion Injury in Mice via STING/AMPK Signaling Pathway
To explore the effects and mechanisms of sevoflurane anesthesia on hepatic ischemia-reperfusion injury(HIRI)in mice,healthy adult male C57 mice were randomly divided into three groups,including sham group(Sham),HIRI+pentobarbital sodium group(HIRI+Pent),and HIRI+sevoflurane group(HIRI+Sevo),10 in each group.The mouse model of partial(70％)HIRI was constructed by laparotomy.After liver ischemia for 60 min and reperfusion for 3 h,mice were sacrificed for sample collection.The pathological damage of liver tissue was observed with hematoxylin-eosin(HE)staining,the content of myeloperoxidase(MPO)was detected by immunofluorescence staining,and apoptosis in tissue was detected using the terminal deoxynu-cleotidyl transferase(TdT)-mediated dUTP-biotin nick end labeling(TUNEL)method.The expression of in-flammation-related factors was detected by both enzyme-linked immunosorbent assay(ELISA)and polymerase chain reaction(PCR).The expression of stimulator of interferon genes(STING),AMP-activated protein kinase(AMPK)and other related proteins was detected by Western-blot.Serum alanine transaminase(ALT),aspar-tate transaminase(AST)and lactate dehydrogenase(LDH)were detected by biochemical analyzer.Meanwhile,the contents of reduced glutathione(GSH),lipid peroxide malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by thiobarbituric acid(TBA)colorimetry,xanthine oxidase method,and dithio-dinitro-benzoic acid method,respectively.The results showed that,compared with mice in Sham group,after ische-mia-reperfusion,mice in HIRI+Pent group had significantly increased serum ALT and AST levels,large in-farcted area in liver tissue,significantly enhanced apoptosis elevated STING and nuclear factor-KB(NF-κB)expression levels,significantly decreased AMPK expression,significantly increased levels of inflammatory factors tumor necrosis factor-a(TNF-a),interleukin(IL)-1β,IL-6,IL-18,and MPO,and significantly dif-ferent levels of the oxidative stress markers GSH,MDA and SOD.However,after ischemia-reperfusion,mice in HIRI+Sevo group exhibited alleviated degrees of all the above changes,with statistical significance(P＜0.05).The study demonstrated that sevoflurane can partially reduce HIRI in mice through STTNG/AMPK signaling pathway.
sevofluranehepatic ischemia-reperfusion injury(HIRI)stimulator of interferon genes(STING)AMP-activated protein kinase(AMPK)
国家科技期刊平台
NSTL
万方数据
