Protective effect and mechanism of dexmedetomidine on lung injury in diabetic mice with myocardial ischemia reperfusion

Objective:To evaluate the protective effect of dexmedetomidine and its mechanism on the lung after myocardial ischemia reperfusion in diabetic mice.Methods:Adult diabetic db/db mice aged 15 weeks were selected.The sham operation group(S group),ischemic reperfusion group(IR group),dexmedetomidine post-treatment group(POST-D)and dexmedetomidine pre-treatment group(PRE-D)were set respectively.The IR group of mice underwent ligation of anterior descending branch of left coronary artery for 30min and readministration for 120min.The post-D group and the pre-D group were intraperitoneally injected with 50 ug/kg DEX before surgery and during reperfusion,respectively.Orbital blood was extracted at 120min of reperfusion,serum levels of creatine kinase isoenzyme MB and inflammatory cytokines IL-6,IFN-γand IL-10 were detected,then mice were sacrificed and lung tissue was taken,the ratio of wet and dry weight(W/D)was determined,lung histopathological morphology was observed under light microscope,superoxide dismutase(SOD)and malondialdehyde(MDA)contents were determined,Western Blot was used to detect the expressions of Sirt1,GRP78 and CHOP in lung tissue.Results:Compared with the S group,the IR group rats had severe lung injury,including increased lung W/D value,increased serum CK-MB、IL-6 and IFN-γlevels,decreased serum IL-10,increased serum MDA content,decreased SOD activity,down-regulated Sirt1 expression,up-regulated GRP78 and CHOP expression.Compared with IR group,lung histopathological injury was reduced in post-D group and pre-D group,lung W/D value was decreased,serum CK-MB、IL-6 and IFN-γlevels were decreased,serum IL-10 was increased,serum MDA content was reduced,SOD activity was rised,the expression of Sirt1 was up-regulated,and GRP78 and CHOP were down-regulated.Compared with the post-D group,the degree of lung tissue injury in the pre-D group was reduced,but the differences in various indicators were not statistically significant.Conclusion:Dexmedetomidine can alleviate acute lung injury after myocardial ischemia reperfusion in diabetic mice,and the mechanism may be related to the up-regulation of Sirt1 and the inhibition of endoplasmic reticulum stress.