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-γ levels, 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-γ levels 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 stres