Effect of oxycodone hydrochloride injection on focal cerebral ischemia-reperfusion injury in rats / 中华急诊医学杂志

ABSTRACT

Objective:To investigate the effect of oxycodone hydrochloride injection pretreatment on focal cerebral ischemia-reperfusion injury in rats.Methods:Seventy-two male SD rats weighing 200-250 g were randomly divided into 3 groups( n=24 each group): sham operation group (sham group), focal cerebral I/R group (I/R group), and oxycodone hydrochloride injection group (Oxy group). Focal cerebral I/R was induced by middle cerebral artery occlusion for 2 h followed by reperfusion. In the Oxy group, oxycodone hydrochloride 0.5 mg/kg was injected iv at 5 min before ischemia. While the same volume of saline (1 mL) was injected in the sham group and I/R group. The neurological deficit score (NDS) was assessed at 24 h of reperfusion, the rats were then sacrificed, and their brains were immediately removed for determination of brain water content and the infarct volume, and the histopathological changes were observed after HE staining. The levels of cytokines (TNF-α, IL-1β and IL-10) in the ischemia cortex were quantified by ELISA. MPO activity in the ischemia cortex was assessed. Western blot was used to detect the expression of NF-κB in the ischemia cortex. The data were analyzed using SPSS 20.0 software, multiple-group comparisons were performed using one-way ANOVA, and LSD- t test was used for pairwise comparison between groups. A P<0.05 was considered statistically significant different. Results:Compared with the sham group, NDS, brain water content, relative infarction volume and rate of nerve cell necrosis were significantly increased in the I/R and Oxy groups (all P<0.05). Levels of TNF-α, IL-1β, IL-10, NF-κB and the activities of MPO were increased in the ischemia cortex (all P<0.05). Compared the Oxy group with the I/R group, NDS, brain water content, relative infarction volume and rate of nerve cell necrosis were significantly decreased [(1.7±0.9) vs (2.6±1.1);(79.2±2.4)% vs (84.7±4.2)%; (23.0±5.4)% vs (34.8±6.0)%; (25.2±12.4)% vs (54.8±14.8)%, all P<0.05]. The levels of TNF-α, IL-1β, relative expression of NF-κB, and the activities of MPO were significantly decreased in the ischemia cortex [(4.4±1.2) pg/mg vs (6.5±1.2) pg/mg; (5.4±0.7) pg/mg vs (7.8±0.8) pg/mg; (0.83±0.11) vs (1.23±0.33); (0.27±0.09) U/g vs (0.36±0.14) U/g, all P<0.05] , while the concentration of IL-10 was significantly increased [(20.9±4.5) pg/mg vs (9.2±1.6) pg/mg, t=6.036, P=0.000 1]. Conclusions:Oxycodone hydrochloride can attenuate focal cerebral I/R injury through inhibiting NF-κB activity.