右美托咪定预处理对视网膜缺血再灌注损伤的保护效应及机制研究

Protective Effect and Mechanism of Dexmedetomidine Pretreatment on Retinal Ischemia-reperfusion Injury

目的:探究右美托咪定预处理对视网膜缺血再灌注损伤的保护效应及机制研究。方法:随机挑选30只雄性大鼠,分为健康组、缺血组和预处理组,每组各10只。健康组大鼠各项指标均正常,缺血组采用高眼压法制造的大鼠视网膜缺血再灌注模型,预处理组对缺血组小鼠进行了右美托咪定预处理。分别于缺血前15 min作用及再灌注前5 min左右,健康组及缺血组按照5 mL/kg大鼠体重进行生理盐水灌注,预处理组对缺血组小鼠按照25μg/kg大鼠体重进行了右美托咪定预处理灌注。比较三组大鼠于再灌注24 h时的视网膜电图(ERG)、细胞凋亡指数(AI)、促凋亡因子(Bax)、抑凋亡因子(Bcl-2)表达水平、肿瘤坏死因子(TNF-α)及白细胞介素-6 (IL-6)表达水平。结果:健康组ERG显著优于缺血组,缺血组ERG显著优于预处理组,三组组间比较差异有统计学意义(F=1 296.98、667.99,P<0.05);健康组AI显著优于缺血组,缺血组AI显著优于预处理组,三组组间比较差异有统计学意义(F=43.32,P<0.05);三组大鼠Bax、Bcl-2、TNF-α、IL-6比较,差异有统计学意义(F=50.09、54.04、113.06、105.19,P<0.05)。结论:右美托咪定可能通过促进Bcl-2表达、抑制Bax表达以改善细胞凋亡指数,同时能够抑制TNF-α、IL-6表达,降低视网膜缺血再灌注损伤炎症效应,进而改善视网膜缺血再灌注损伤发挥保护作用。

Objective:To investigate the protective effect and mechanism of dexmedetomidine pretreatment on retinal ischemia-reperfusion injury.Methods:30 male rats were randomly selected and divided into healthy group,ischemic group and pretreatment group,with 10 rats in each group.All indexes were normal in the healthy group of rats,and the ischemic group used a rat retinal ischemia-reperfusion model made by the high intraocular pressure method,and the pretreatment group was pretreated with dexmedetomidine for the ischemic group of mice.The healthy and ischemic groups were perfused with saline at 5 mL/kg rat body weight at 15 min before ischemia and about 5 min before reperfusion,respectively,and the pretreatment group was perfused with dexmedetomidine at 25μg/kg rat body weight in the ischemic group.The expression levels of electroretinogram(ERG),apoptosis index(AI),pro-apoptotic factor(Bax),anti-apoptotic factor(Bcl-2),tumor necrosis factor(TNF-α)and interleukin-6(IL-6)were compared among the three groups of rats at 24 h of reperfusion.Results:The ERG of the healthy group was significantly better than that of the ischemic group,and the ERG of the ischemic group was significantly better than that of the pretreated group,with statistically significant differences between the 3 groups(F=1296.98,667.99,P<0.05).The AI in the healthy group was significantly better than that in the ischemic group,and the AI in the ischemic group was significantly better than that in the pretreatment group,with statistically significant differences(F=43.32,P<0.05).There was a statistically significant difference in the comparison of Bax,Bcl-2,TNF-α,and IL-6 among the 3 groups(F=50.09,54.04,113.06,105.19,P<0.05).Conclusion:Dexmedetomidine may play a protective role by promoting Bcl-2 expression and inhibiting Bax expression to improve the apoptotic index,as well as inhibiting TNF-αand IL-6 expression to reduce the inflammatory effect of retinal ischemia-reperfusion injury,thus improving retinal ischemia-reperfusion injury.