Adipolin/CTRP12 protects against LPS-induced ARDS by up-regulating alveolar epithelial sodium channel in mice
10.3969/j.issn.1000-4718.2016.07.016
- VernacularTitle:Adipolin／CTRP12对LPS致ARDS小鼠的保护作用及肺泡上皮钠离子通道的调节
- Author:
Xumao TANG
;
Di QI
;
Daoxin WANG
- Publication Type:Journal Article
- Keywords:
Acute respiratory distress syndrome;
Adipolin/CTRP12;
Epithelial sodium channel;
PI3K/Akt signaling pathway
- From:
Chinese Journal of Pathophysiology
2016;32(7):1252-1258
- CountryChina
- Language:Chinese
-
Abstract:
[ ABSTRACT] AIM:To investigate the effect of adipolin/CTRP12 in LPS-induced acute respiratory distress syn-drome (ARDS) and its potential regulation on alveolar epithelial sodium channel (ENaC) in mice.METHODS:C57BL/6J mice (n=40) 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 of the lung tissues were evaluated by HE staining.The alveolar fluid clearance ( AFC) was measured by Evans blue-marked albumin, and the concentrations of total protein in bronchoalveolar lavage fluid ( BALF) were assessed by bicinchoninic acid ( BCA) method.In BALF, the levels of IL-1βand TNF-αwere determined by ELISA, and the activity of myeloperoxidase ( MPO) was detected by an MPO assay kit.The total cell counts and polymorphonuclear neutrophil ( PMN) counts in the BALF were analyzed by Gi-emsa staining.The mRNA levels of α-ENaC were assessed by qPCR, while the protein levels of α-ENaC and p-Akt were determined by Western blot.RESULTS: Compared with control group, the classic ARDS pathological changes were ob-served in the mice in LPS group, manifesting by severe pathological lung injury (P<0.05), increases in W/D weight rati-o, total protein levels, cell counts, MPO activitiy, and IL-1βand TNF-αlevels in the BALF, and decrease in AFC ( P<
0.05), accompanied by down-regulated levels of α-ENaC and p-Akt in the lung tissues (P<0.05).The deteriorating effects triggered by LPS were significantly reversed by administration of adipolin.However, PI3K inhibitor wortmannin can-celed the beneficial effects of adipolin on LPS-induced ARDS, as evidenced by aggravated lung injury, increased levels of W/D weight ratio, protein levels, cell counts, MPO activity, and IL-1βand TNF-αlevels in the BALF (P<0.05), and decreased levels of AFC,α-ENaC and p-Akt in the lung tissues.CONCLUSION:Adipolin protects against LPS-induced ARDS in the mice by up-regulatingα-ENaC and enhancing AFC via PI3K/Akt signal pathway.
