摘要
目的通过玻璃体腔内注射雷珠单抗,观察小鼠氧诱导视网膜病变模型(OIR)中视网膜色素上皮衍生因子(PEDF)和高迁移族率蛋白1(HMGB1)的表达,探讨雷珠单抗对缺血缺氧性视网膜病变的保护作用和机制。方法取7日龄健康级C57/B6J新生小鼠60只,随机分为正常对照组、OIR组、OIR+雷珠单抗组,每组20只。正常对照组于出生后7 d在正常环境中饲养至17 d,OIR组及OIR+雷珠单抗组于出生后7 d放置于体积分数(75±2)%氧气中,在此环境中饲养至12 d,之后在正常常氧环境中饲养至17 d。期间OIR+雷珠单抗组于12 d行右眼玻璃体腔内药物注射雷珠单抗1μl,各组小鼠均于17 d用1%戊巴比妥钠腹腔注射过量麻醉处死。行HE染色观察细胞形态及新生血管情况;行Western blot检测视网膜中PEDF、HMGB1的表达。结果HE染色结果显示:正常对照组视网膜各层结构清晰,未见血管内皮细胞核突破内界膜;OIR组视网膜各层结构排列紊乱,可见内皮细胞核突破内界膜。Western blot结果显示:与正常对照组比较,OIR组PEDF在视网膜中表达量下降,HMGB1在视网膜中表达量升高,差异均有统计学意义(均P<0.05);OIR+雷珠单抗组与OIR组比较,PEDF表达量上调,HMGB1表达量下降,差异均有统计学意义(均P<0.05)。结论OIR模型中PEDF在视网膜中表达量下降,HMGB1在视网膜中表达量上升,两者可能共同参与视网膜新生血管形成及ROP的发展;通过玻璃体腔注射雷珠单抗后,PEDF在视网膜中表达量上升,HMGB1在视网膜中表达量下降,表明雷珠单抗可能通过调节PEDF和HMBG1的表达从而抑制氧诱导小鼠视网膜新生血管形成。
Objective To observe the expression of retinal pigment epithelium-derived factor(PEDF)and high mobility group rate protein 1(HMGB1)in a mouse model of oxygen-induced retinopathy(OIR)by intravitreal injection of razumab,and to investigate the protective effect and mechanism of razumab on ischemic-hypoxic retinopathy.Methods A prospective case-control study.Sixty 7-day-old healthy grade C57/B6J neonatal mice were randomly divided into normal control group,OIR group and OIR+rezumab group,20 mice in each group.The normal control group was kept in a normal environment until the 17th day after birth,while the OIR and OIR+Rezumab groups were placed in oxygen at a volume fraction of(75±2)%on the 7th day after birth and kept in this environment until the 12th day,and then kept in a positive normoxic environment until the 17th day.During this period,the OIR+Rezumab group received intravitreal injection of ralizumab in the right eye on the 12th day.The mice in all groups were anesthetized with 1%sodium pentobarbital intraperitoneal injection on the 17th day.The expression of PEDF and high mobility group protein 1(HMGB1)in the retina was detected by Western blot.Results Theresults of hematoxylin eosin(HE)staining showed that the structure of the retinal layers in the normal control group was clear,and the nuclei of endothelial cells did not break through the inner boundary membrane.The structure of the retinal layers in the OIR group was disordered,and the nuclei of endothelial cells broke through the inner boundary membrane.The differences were statistically significant(all P<0.05).PEDF expression was upregulated and HMGB1 expression was decreased in the OIR+rezumab group compared with the OIR group(all P<0.05).Conclusions PEDF expression decreased and HMGB1 expression increased in the retina of the OIR model,and both may be jointly involved in retinal neovascularization and the development of retinopathy of prematurity(ROP).PEDF expression increased and HMGB1 expression decreased in the retina after injecting ranibizumab through the vitreous cavity,which indicated that ranibizumab may regulate the expression of PEDF and HMBG1 and thus inhibit oxygen-induced retinal neovascularization in mice.
作者
郭净
刘向玲
苏邵波
Guo Jing;Liu Xiangling;Su Shaobo(The Third Clinical College of Xinxiang Medical University,Xinxiang 453000,China)
出处
《临床眼科杂志》
2023年第4期360-364,共5页
Journal of Clinical Ophthalmology
关键词
早产儿视网膜病变
氧诱导视网膜病变
色素上皮衍生因子
高迁移族率蛋白1
Retinopathy of prematurity
Oxygen-induced retinopathy
Pigment epithelium-derived factor
High mobility group rate protein 1
