依达拉奉对氧诱导视网膜病变乳鼠的作用及其机制研究*

Free radical scavenger edaravone inhibits neovascularization in oxygen-induced retinopathy in suckling rats*

摘要:

目的?探讨自由基清除剂依达拉奉对氧诱导视网膜病变乳鼠的抑制作用及可能机制。方法?将60只乳鼠根据随机数字表法分为正常对照组、高氧诱导组和药物治疗组，每组20只。高氧诱导复制视网膜病变乳鼠模型，采用黄嘌呤法测定视网膜超氧化物歧化酶（SOD）活力和丙二醛（MDA）含量，苏木精-伊红（HE）染色观察视网膜病理变化，二磷酸腺苷（ADP）染色测定视网膜无灌注区面积，免疫组织化学染色测定视网膜中血管内皮生长因子（VEGF）、CD34的表达。结果?3组乳鼠体重在不同时间、不同组间、变化趋势上有差异（P?<0.05）。3组乳鼠视网膜SOD、MDA，以及VEGF和CD34光密度值比较，差异有统计学意义（P?<0.05）；与正常对照组比较，高氧诱导组乳鼠视网膜SOD活力降低（P?<0.05），MDA含量升高（P?<0.05），VEGF、CD34累积光密度值和平均光密度值升高（P?<0.05）；与高氧诱导组比较，药物治疗组乳鼠视网膜SOD活力升高（P?<0.05），MDA含量降低（P?<0.05），VEGF、CD34累积光密度值和平均光密度值降低（P?<0.05）。药物治疗组ADP染色无灌注区面积小于高氧诱导组（P?<0.05）。HE染色结果显示，正常对照组乳鼠视网膜未见病变；高氧诱导组乳鼠视网膜见大量血管增生、管腔扩张、出血；药物治疗组视网膜病变较高氧诱导组轻，未见出血。结论?依达拉奉对氧诱导视网膜病变乳鼠具有保护作用，可抑制视网膜氧化应激反应和新生血管形成。

Abstract:

Objective To explore the therapeutic effect and possible mechanism of free radical scavenger edaravone on oxygen-induced retinopathy in suckling rats. Methods According to the random number method, 60 suckling rats were divided into normal control group, hyperoxia induction group and drug treatment group, with 20 rats in each group. Hyperbaric oxygen treatment was applied to establish the retinopathy of prematurity (ROP) model. The retinal superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were determined by xanthine oxidase method. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of the retina. Adenosine diphosphate (ADP) staining was used to determine the non-perfusion area of the retina. Immunohistochemical staining was used to determine the expression of vascular endothelial growth factor (VEGF) and CD34 in the retina. Results The weights of the three groups of suckling rats were compared at each time point, and the repeated measures design was used to analyze the variance. The body weight of the suckling rats at different time points was different (F?=?19.055, P?=?0.000). There were also differences in the weight of the suckling rats among the three groups (F?=?31.229, P?=?0.000). Besides, the changing trend of the weights of suckling rats in each group was different (F?=?3.688, P?=?0.000). There were statistically significant differences in retinal SOD activity, MDA content, as well as optical density of VEGF and CD34 among the three groups of suckling rats (P?