基于转录组学分析昆布多糖对C57BL/6小鼠非增生性糖尿病视网膜病变的影响  

Effects of laminarin on non-proliferative diabetic retinopathy in C57BL/6 mice based on transcriptomics analysis

作　　者：张蕾[1,2] 张素梅 杨振 胡韦康 白红枚 周文静 王子涵 李名聪 张胜权[3] 廖荣丰[1] Zhang Lei;Zhang Sumei;Yang Zhen;Hu Weikang;Bai Hongmei;Zhou Wenjing;Wang Zihan;Li Mingcong;Zhang Shengquan;Liao Rongfeng(Dept of Ophthalmology,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;Dept of Ophthalmology,Fuyang People′s Hospital of Anhui Medical University,Fuyang 236012;Dept of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Anhui Medical University,Hefei 230032;Dept of Pathology,Anhui Medical University Affiliated Hefei Hospital(The Second People′s Hospital of Hefei),Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院眼科,合肥230022 [2]安徽医科大学附属阜阳市人民医院眼科,阜阳236012 [3]安徽医科大学基础医学院生物化学与分子生物学教研室,合肥230032 [4]安徽医科大学附属合肥医院(合肥市第二人民医院)病理科,合肥230022

出　　处：《安徽医科大学学报》2025年第3期392-398,共7页Acta Universitatis Medicinalis Anhui

基　　金：安徽省高校科研项目(编号:2022AH050651);安徽医科大学校科研基金项目(编号:2022xkj107);蚌埠医学院科技项目自然科学重点项目(编号:2022byzd196)。

摘　　要：目的采用高通量测序技术(RNA-seq)探讨昆布多糖(LAM)对非增生性糖尿病视网膜病变(NPDR)的影响。方法采用链脲佐菌素(STZ)腹腔注射建立糖尿病模型,观察LAM对糖尿病小鼠的影响。将C57BL/6小鼠随机分为对照(Control)、模型(Model)、昆布多糖治疗(LAM)组,每组8只小鼠。在建模8周后,LAM组接受为期4周的LAM腹腔注射治疗。记录3组小鼠血糖体质量变化,HE染色检查视网膜病变情况,采用RNA-seq挖掘STZ及LAM作用下糖尿病视网膜病变(DR)的关键差异基因(DEGs)。结果使用STZ可以成功建立DR模型,而LAM可以在一定程度上降低糖尿病小鼠血糖并改善糖尿病小鼠视网膜结构疏松的病理形态。经过RNA-seq对DEG挖掘发现与Control组相比,Model组小鼠视网膜共有214个DEGs,通过富集分析发现DR可通过PI3K-Akt信号通路加重病变程度。Model组与LAM组小鼠视网膜共有DEGs 42个,富集后显示LAM通过中性粒细胞胞外陷阱通路改善其病变程度。早期生长反应因子1(Egr1),FBJ骨肉瘤致癌基因(Fos),核受体亚家族4A成员1(Nr4a1),盐诱导激酶1(Sik1)受STZ调节,而LAM能显著回调其表达,可能与LAM对糖尿病视网膜病变的治疗密切相关。结论DEG可通过PI3K-Akt信号通路加重糖尿病视网膜病变程度。LAM可以通过中性粒细胞胞外陷阱通路减轻糖尿病视网膜病变,Egr1、Fos、Nr4a1、Sik1是LAM治疗STZ诱导DR的关键基因。Objective To investigate the effect of laminarin(LAM)on nonproliferative diabetes retinopathy by high throughput sequencing(RNA-seq).Methods The diabetes model was established by intraperitoneal injection of streptozotocin(STZ),and the effect of LAM on diabetic mice was observed.C57BL/6 mice were randomly divided into three groups:Control group,Model group,and LAM group,with 8 mice in each group.After 8 weeks of modeling,the LAM group received a 4-week intraperitoneal injection of LAM treatment.Changes in blood glucose and body weight of the three groups of mice were recorded,HE staining was performed to examine retinal lesions,and RNA-seq was used to identify differentially expressed genes(DEGs)in diabetic retinopathy(DR)under the action of STZ and LAM.Results STZ successfully established the model of DR,and LAM reduced the blood sugar in diabetic mice to a certain extent and improved the pathological morphology of retinal structural looseness in diabetic mice.After RNA-seq analysis of DEGs,it was found that there were a total of 214 DEGs in the retina of the Model group mice compared to the Control group.Enrichment analysis revealed that DR could exacerbate the lesions through the PI3K Akt signaling pathway.There were a total of 42 DEGs in the retina of the Model group and LAM group mice,and enrichment showed that LAM improved the lesions through the neutrophil extracellular trap pathway.Early growth response factor 1(Egr1),FBJ osteosarcoma oncogene(Fos),nuclear receptor subfamily 4A member 1(Nr4a1),and salt-induced kinase 1(Sik1)were regulated by STZ,and LAM significantly regulated their expression,which might be closely related to LAM′s treatment of diabetic retinopathy.Conclusion DEGs can exacerbate the severity of diabetic retinopathy via the PI3K-Akt signaling pathway.LAM can mitigate diabetic retinopathy via the neutrophil extracellular trap pathway.Egr1,Fos,Nr4a1,and Sik1 are key genes involved in LAM treatment of STZ-induced DR.

关 键 词：高通量测序 昆布多糖 糖尿病视网膜病变 C57BL/6 

分 类 号：R774.1[医药卫生—眼科]