Dexmedetomidine Attenuates Lung Injury In Obstructive Jaundice Rats By PI3K/Akt/HIF-1α Signaling Pathway

Objective:To evaluate the role of the phosphatidylinositol 3-kinase-protein-ser-ine-threonine kinases-hypoxia inducible factor-1αsignaling pathway in the protection by dexmedetomidine against lung injury in obstructive jaundice rats.Methods:Forty male SPF Wistar rats,weighing 220-270g,aged 7-9 weeks,were randomized into 4 groups（n=10）using a random number table:Sham group（S group）,obstructive jaundice group（OJ group）,dexmedetomidine group（D group）and combined dexmedetomidine and LY294002 group（DL group）.Group D was slowly injected with DEX(100ug·kg^-1)in the abdominal cavity 72 hours after model manufacture.The DL group was pumped into LY294002(0.3mg·kg^-1)after 72h modeling,and then injected with Dex(100ug·kg^-1).72 hours after surgery,the Sham group and OJ group’s blood were collected from the carotid artery and taked 2 parts of the left lobe lung tissues.Group D and DL were given dexmedetomidine for 3hours after surgery,and then collected the blood and lung tissue.HE staining for pathological changes in lung tissue.The expression of phospho-Akt（p-Akt）,HIF-1α（hypoxia inducible factor-1α）、Akt mRNA、HIF-1αmRNA、interleukin-6（IL-6）and tumor necrosis factor-alph（TNF-α）were quantified using western blot、RT-PCR and ELISA.Results:As compared with the DL group,the lung injury score was slightly decreased in the OJ group.Compared with the S group,the express of the HIF-1α、p-Akt、Akt mRNA、HIF-1αmRNA were significantly increased in OJ group.Compared to OJ group,the HIF-1α、p-Akt、Akt mRNA、HIF-1αmRNA expression were up-regulated in the D group,the express of the HIF-1α、p-Akt、Akt mRNA、HIF-1αmRNA were insignificance in the DL group.Compared to the D group,the HIF-1α、p-Akt、Akt mRNA、HIF-1αmRNA expression were down-regulated.Regarding the expression of inflammatory factors in serum,compared with S group,the expression of IL-6 and TNF-αin OJ group and D group was up-regulated;Compared with the OJ group,the expression of IL-6 and TNF-αdecreased in the D group and the DL group;compared with group D,IL-6 and TNF-αexpression were up-regulated in DL group.Conclusion:Dexmedetomidine can partially attenuate lung injury in obstructive jaundice rats by PI3K/Akt/HIF-1αsignaling pathway;Dexmedetomidine can reduce the expression of inflammatory factors IL-6 and TNF-αin obstructive jaundice rats.