氢吗啡酮预处理对大鼠视网膜缺血-再灌注损伤的影响

目的观察氢吗啡酮预处理对大鼠视网膜缺血-再灌注损伤的影响,并探讨其作用机制。方法SPF级SD大鼠48只,随机分为假手术组(C组)、缺血-再灌注组(IR组)、氢吗啡酮组(H组)和吗啡组(M组),每组12只。采用前房加压灌注的方法制备视网膜缺血-再灌注损伤模型。于缺血前15 min,H组颈内静脉注射氢吗啡酮0.1mg/kg,M组注射吗啡1mg/kg,C组和IR组注射等容量生理盐水。再灌注24 h后,取大鼠视网膜组织,采用HE染色法观察病理学变化,测定视网膜内层厚度及全层厚度;采用TUNEL法计算细胞凋亡指数(AI);采用免疫组化法检测Bax、Bcl-2、caspase-3蛋白含量;采用ELISA法检测TNF-α、IL-6浓度;采用硫代巴比妥酸及黄嘌呤氧化酶法分别检测MDA浓度和SOD活性。结果与C组比较,IR组视网膜出现病理学损伤,AI明显升高(P<0.05);Bax、caspase-3蛋白含量明显升高,Bcl-2蛋白含量和Bcl-2/Bax比值明显降低(P<0.05);TNF-α、IL-6和MDA浓度明显升高(P<0.05),SOD活性明显减弱(P<0.05)。与IR组比较,H组和M组视网膜组织病理学损伤明显减轻,AI明显降低(P<0.05);Bax、caspase-3蛋白含量明显降低,Bcl-2蛋白含量明显升高,Bcl-2/Bax比值明显升高(P<0.05);TNF-α、IL-6和MDA浓度明显降低,SOD活性明显增强(P<0.05)。结论氢吗啡酮可减轻大鼠视网膜缺血-再灌注损伤,其机制可能与改善视网膜细胞凋亡、炎症反应及氧化应激相关。

Effects of hydromorphone pre-administration on retinal ischemia-reperfusion injury in rats

Objective To observe the effects of hydromorphone pre-administration on retinal ischemia-reperfusion injury(RIRI)in rats and to explore its mechanism.Methods Forty-eight SPF SD rats were randomly divided into four groups:control group(group C),ischemia-reperfusion group(group IR),hydromorphone pre-administration group(group H)and morphine pre-administration group(group M),with 12 rats in each group.The rat model of RIRI was established by anterior chamber pressure repefusion.Hydromorphone 0.1 mg/kg was intravenously injected in group H,morphine 1 mg/kg was intravenously injected in group M and the equal volume of normal saline was intravenously injected in group C and group IR 15 min before ischemia.After 24 h of reperfusion,the rat retinal tissue was taken,and the pathological changes were observed by HE staining,and the thickness of the inner layer and the whole layer of the retina were measured.The TUNEL method was used to calculate the apoptosis index(AI).Content of Bax,Bcl-2 and caspase-3 protein were detected by immunohistochemistry.TNF-αand IL-6 concentrations were measured by ELISA.Thiobarbituric acid and xanthine oxidase methods were used to detect MDA concentration and SOD activity,respectively.Results Compared with group C,the pathological damage of retina in rats was significantly increased,AI was significantly increased(P<0.05),the expression of Bax and caspase-3 were significantly increased,the expressions of Bcl-2 and Bcl-2/Bax ratio were significantly decreased(P<0.05),and the levels of TNF-α,IL-6,MDA were significantly increased,and the level of SOD was significantly decreased in group IR(P<0.05).Compared with group IR,the pathological damage of retina in rats was significantly decreased and AI were significantly decreased(P<0.05),the expression of Bax,caspase-3 were significantly decreased,the expressions of Bcl-2 and Bcl-2/Bax ratio were significantly increased(P<0.05),the levels of TNF-α,IL-6,MDA were significantly decreased and the level of SOD significantly increased in groups H and M(P<0.05).Conclusion Hydromorphone can attenuate RIRI in rats,and its mechanism may be related to the improvement of retinal cell apoptosis,inflammatory response and oxidative stress.