Adipolin/CTRP12 Protects Against LPS-induced ARDS By Up-regulating Alveolar Epithelial Sodium Channel In Mice

ObjectiveTo investigate the effect of Adipolin/CTRP12 in LPS-induced ARDS and its potential regulation on alveolar epithelial sodium channel(ENaC)in mice.MethodsForty C57BL/6J mice were randomly divided into control group,LPS group,Adipolin group and wortmannin(PI3K inhibitor)group with 10 mice in each group using random number table.The pathological changes in lung tissue were evaluated by HE staining;The alveolar fluid clearance(AFC)was evaluated by Evans blue-marked albumin;the concentrations of total protein in bronchoalveolar lavage fluid(BALF)were assessed by BCA(bicinchoninic acid).In BALF,the levels of IL-1? and TNF-? were determined by ELISA and myeloperoxidase(MPO)activities were measured by MPO assay kit.The total cell counts and polymorphonuclear neutrophil(PMN)counts of BALF were detected by Giemsa staining.The transcription levels of ?-ENaC mRNA were assessed by qPCR while the protein levels of ?-ENaC and p-Akt were measured by Western blot.ResultsCompared with mice in control group,classic ARDS pathological changes were observed in mice of LPS group,manifesting by severe pathological lung injury(P<0.05),increases in W/D weight ratio,total protein levels,cell counts,MPO activities,IL-1? and TNF-? levels in BALF and decrease in AFC(P<0.05),accompanied by down-regulated levels of ?-ENa C and p-Akt in lung tissues(P<0.05).The deteriorative effects triggered by LPS were significantly reversed by administration of Adipolin.However PI3 K inhibitor,wortmannin,canceled the beneficial effects of Adipolin on LPS-induced ARDS,as evident by aggravated lung injury,increased levels of W/D weight ratio,protein levels,cell counts,MPO activities,IL-1? and TNF-? levels in BALF(P<0.05)and decreased levels of AFC,?-ENaC and p Akt in lung tissues.ConclusionAdipolin can protect against LPS-induced ARDS in mice by up-regulating ?-ENaC and enhancing AFC via PI3K/Akt mechanism.