Roles of PI3 K/Akt and JAK2/STAT3 signaling pathways in protection of SO2 against limb ischemia/reperfusion-induced acute lung injury in rats / 中国病理生理杂志

ABSTRACT

AIM:To investigate the role of PI3K/Akt and JAK2/STAT3 pathways in the protection of sulfur dioxide (SO2) against limb ischemia/reperfusion (I/R)-induced acute lung injury (ALI) in rats.METHODS:ALI was induced by limb I/R in the SD rats.Na2 SO3 (0.54 mmol/kg, ip)/NaHSO3 (0.18 mmol/kg, ip) as SO2 donor was injec-ted at 20 min before reperfusion.The inhibitors of JAK2/STAT3 and PI3K/Akt pathways, Stattic (3 mg/kg, iv) and LY294002 (40 mg/kg, iv), respectively, were injected at 1 h before reperfusion.Peripheral blood and lung tissues were collected for determining the contents of the cytokines, the protein levels of the molecules related to the signaling pathways, apoptosis and histopathologic changes by ELISA, TUNEL and Western blot.RESULTS:Compared with control group, the content of MDA, the activity of MPO, lung coefficient, apoptotic index, cytokine expression, and the protein levels of p-Akt and p-STAT3 in I/R group all increased significantly, and administration of Na2 SO3/NaHSO3 attenuated the damage in the lung.Besides, the results of Western blot showed that the rat lung tissues expressed p-STAT3 protein and p-Akt pro-tein.After I/R, the protein levels of p-STAT3 and p-Akt were increased.After using Na2 SO3/NaHSO3 , p-Akt was in-creased, but p-STAT3 was decreased (P<0.05).CONCLUSION:Both JAK2/STAT3 and PI3K/Akt pathways are like-ly involved in the protective effect of SO2 against limb I/R-induced ALI in rats.The activation of JAK2/STAT3 signaling pathway increases I/R injury.Reversely, the activation of PI3K/Akt signaling pathway reduces I/R injury.Besides, JAK2/STAT3 and PI3K/Akt signaling pathways may have crosstalk during I/R-induced ALI and JAK2/STAT3 pathway may have an impact on the P13K/Akt pathway.