Dexmedetomidine Alleviates Lung Oxidative Stress Injury Induced by Ischemia-Reperfusion in Diabetic Rats via the Nrf2-Sulfiredoxin1 Pathway

Abstract

Oxidative stress injury (OSI) is an important pathological process in lung ischemia-reperfusion injury (LIRI), and diabetes mellitus (DM) can exacerbate this injury. Dexmedetomidine protects against LIRI by reducing OSI. However, the effect of dexmedetomidine on LIRI under diabetic conditions remains unclear. Therefore, this study is aimed at exploring the effects and mechanisms of dexmedetomidine on OSI induced by LIRI in diabetic rats. Rats were randomly divided into control+sham (CS), DM+sham (DS), control+ischemia-reperfusion (CIR), DM+ischemia-reperfusion (DIR), and DM+ischemia-reperfusion+dexmedetomidine (DIRD) groups ( $n=6$ ). In the CS and DS groups, the nondiabetic and diabetic rats underwent thoracotomy only without LIRI. In the CIR, DIR, and DIRD groups, LIRI was induced through left hilum occlusion for 60 min, followed by reperfusion for 120 min in nondiabetic and diabetic rats, and rats in the DIRD group were administered dexmedetomidine (3, 5, and 10 μg/kg). Compared with those in the CS group, the OSI, lung compliance, apoptosis, and oxygenation indices deteriorated in the DS group ( $P<0.05$ ), and these indices were further aggravated in the CIR and DIR groups ( $P<0.05$ ), being the worst in the DIR group ( $P<0.05$ ). Compared to those of the DIR group, the OSI, lung compliance ( $15.8\pm 2.4$ vs. $11.6\pm 1.7\text{ml}/\text{kg}$ ), apoptosis ( $22.5\pm 2.6$ vs. $51.8\pm 5.7$ ), oxygenation ( $381\pm 58$ vs. $308\pm 78\text{mmHg}$ ), and caspase-3 and caspase-9 protein expression indices were attenuated, and Nrf2 and sulfiredoxin1 protein expression was increased in the DIRD group ( $P<0.05$ ). And the lung injury, oxygenation, OSI, and Nrf2 and sulfiredoxin1 protein expression changed in a concentration-dependent manner. In conclusion, dexmedetomidine alleviated lung OSI and improved lung function in a diabetic rat LIRI model through the Nrf2-sulfiredoxin1 pathway.