IGF-1R抑制剂通过调控自噬抑制碱烧伤小鼠角膜基质纤维化  

IGF⁃1R inhibitor inhibits corneal stromal fibrosis after alkali burn in mice by regulating autophagy

作　　者：程思敏 蒋维艳 颜瑜琳 万珊珊[1] 杨燕宁[1] CHENG Simin;JIANG Weiyan;YAN Yulin;WAN Shanshan;YANG Yanning(Eye Center,Renmin Hospital of Wuhan University,Wuhan 430060,Hubei,China)

机构地区：[1]武汉大学人民医院眼科中心,湖北武汉430060

出　　处：《武汉大学学报（医学版）》2024年第6期657-662,687,共7页Medical Journal of Wuhan University

基　　金：国家自然科学基金青年项目(编号:82101081)。

摘　　要：目的:探究胰岛素样生长因子1-受体(IGF-1R)在碱烧伤小鼠角膜组织的表达情况,以及IGF-1抑制剂(PPP)对小鼠角膜基质纤维化的影响和作用机制。方法:81只C57BL/6J小鼠随机分为对照(Control)组、碱烧伤(AB)组、碱烧伤+溶剂组(DSMO)和碱烧伤+IGF-1R抑制剂组(PPP)。除Control组外,其余三组建立碱烧伤模型。自造模前1 d,PPP组给予2 mol/L PPP滴眼,DMSO组给予相同剂量溶剂,处理14 d。PCR和免疫蛋白印迹检测碱烧伤小鼠角膜组织中IGF-1R的mRNA和蛋白水平。裂隙灯显微镜观察IGF-1R抑制剂干预处理后小鼠角膜混浊情况,HE染色观察角膜组织病理损伤,PCR、Western Blot和免疫荧光染色检测角膜组织α-SMA和LC3mRNA和蛋白表达水平。结果:碱烧伤造模后14 d,与Control组相比,AB组IGF-1R蛋白和mRNA表达量增加;与DMSO组相比,PPP组角膜混浊和组织病理损伤减轻,α-SMA蛋白和mRNA表达水平降低,LC3蛋白和mRNA表达水平增加。结论:抑制IGF-1R可能通过促进自噬,抑制角膜基质纤维化,进而减轻碱烧伤小鼠角膜损伤。Objective:To investigate the expression of insulin‑like growth factor 1 receptor(IGF‑1R)in mice cornea after alkali burn,and to explore the effect and mechanism of IGF‑1R inhibitor(PPP)on corneal fibrosis.Methods:Eighty‑one mice were randomly divided into the control group,alkali burn group(AB),alkali burn+solvent(DMSO)group,and alkali burn+IGF‑1R inhibitor(PPP)group.Except in the control group,the alkali burn models were established in the other three groups.From one day before establishing the model,mice in PPP the group were given 2 mol/L PPP eye drops,and those in the DMSO group were given DMSO eye drops at the same dose for 14 d.PCR and Western blot were used to detect the levels of IGF‑1R mRNA and protein in mice cornea after alkali burn.The slit lamp microscope was used to observe corneal opacity after the intervention of IGF‑1R inhibition.HE staining was used to observe the pathological injury in corneal tissue.PCR,Western Blot,and immunofluorescence staining were used to evaluate the expression ofαsmooth muscle actin(α‑SMA)and LC3 in corneal tissue.Results:At the end of the 14th day after alkali burn,there was an increased trend in the levels of IGF‑1R mRNA and protein of the AB group as compared with the control group.Compared with those in the DMSO group,there were decreased corneal transparency and pathological injury,lower expression levels ofα‑SMA mRNA and protein,as well as higher expression levels of LC3 mRNA and protein in the PPP group.Conclusion:IGF‑1R inhibition may facilitate autophagy and inhibit corneal stromal fibrosis to relieve corneal injury after alkali burn.

关 键 词：胰岛素样生长因子1-受体 角膜碱烧伤 角膜基质纤维化 自噬 

分 类 号：R772.2[医药卫生—眼科]