miR-26a-5p调控PTEN/PI3K/Akt信号通路对高糖诱导视网膜Müller细胞活化及凋亡的影响  

Effects of miR-26a-5p on high glucose-induced retina Müller activation and apoptosis by regulating PTEN/PI3K/Akt signaling pathway

作　　者：唐德荣 杨雨雯 石蕊[3] 刘丹丹 TANG Derong;YANG Yuwen;SHI Rui;LIU Dandan(Department of Ophthalmology,Medical College of Ankang Vocational and Technical College/Ankang Central Hospital,Ankang 725000;Wenzhou Medical University,Wenzhou 325035;Department of Ophthalmology,Shaanxi Provincial People’s Hospital,Xi’an 710068,China)

机构地区：[1]安康市职业技术学院医学院/安康市中心医院眼科,陕西安康725000 [2]温州医科大学,浙江温州325035 [3]陕西省人民医院眼科,陕西西安710068

出　　处：《西安交通大学学报（医学版）》2024年第5期705-711,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省自然科学基础研究计划项目(No.2022JM-571),陕西省人民医院科技发展孵化基金资助项目(No.2021YJY-20)。

摘　　要：目的检测微小RNA-26a-5p(microRNA-26a-5p,miR-26a-5p)对PTEN/PI3K/Akt信号通路及高糖刺激的视网膜Müller细胞凋亡的影响,探讨糖尿病视网膜神经损伤的潜在机制。方法采用不同浓度的葡萄糖刺激视网膜Müller细胞构建糖尿病视网膜神经损伤模型,采用CCK-8及流式细胞仪观察细胞增殖及凋亡情况,细胞转染过表达miR-26a-5p模拟物,Real-time PCR检测miR-26a-5p、PTEN、PI3K、Akt的表达情况,ELISA测定细胞上清液中IL-1β及IL-6的水平,采用Graphpad 8.0软件处理数据。结果高糖刺激视网膜Müller细胞生长活跃,与对照组相比,50 mmol/L高糖刺激Müller细胞活力在12 h、24 h时逐渐增加,48 h时活力减弱,细胞凋亡增加,组间差异有统计学意义(P<0.05)。高糖刺激后视网膜Müller细胞中miR-26a-5p水平下降,PTEN的表达显著升高,PI3K及Akt水平下降,IL-1β及IL-6的水平明显升高,过表达miR-26a-5p后,PTEN水平降低,PI3K/Akt及炎性因子降低,细胞凋亡减少(P<0.01)。结论miR-26a-5p通过调控PTEN/PI3K/Akt的表达,影响炎症因子释放,减轻高糖诱导的视网膜Müller细胞凋亡。Objective To investigate the effects of microRNA-26a-5p(miR-26a-5p)on high glucose-induced retina Müller activation and apoptosis by regulating PTEN/PI3K/Akt signaling pathway,and the potential mechanism of diabetic retinal neurodegeneration.Methods Various concentrations of high glucose were added into rMC-1 culture.CCK-8 and flow cytometry was used to examine cell proliferation and apoptosis respectively.The regulatory effects of miR-26a-5p on the expressions of PTEN,PI3K and Akt were observed by real-time PCR;the expression levels of IL-1βand IL-6 in Müller cells were examined by ELISA.The data were processed by Graphpad 8.0 software.Results Müller cells grew actively in high-glucose stimulation culture.Compared with the control group,the activity of Müller cells stimulated by 50 mmol/L glucose increased gradually at 12 h and 24 h,but decreased at 48 h after stimulation,when Müller cells apoptosis increased.The difference between the groups was statistically significant(P<0.05).The expression of miRNA-26a-5p decreased,that of PTEN increased,and those of PI3K and Akt decreased.Meanwhile,IL-1βand IL-6 levels were significantly increased in Müller cells.miR-26a-5p over-expression alleviated injuries to high glucose stimulated retinal Müller cells by inhibiting PTEN,which upregulated the expression of PI3K/Akt and downregulation of IL-1βand IL-6(P<0.01).Conclusion Upregulating miR-26a-5p protects Müller cells against apoptosis,probably through regulation of PTEN/PI3K/Akt and affecting the production of inflammatory factors.

关 键 词：视网膜MÜLLER细胞 微小RNA-26a-5p(miR-26a-5p) PTEN/PI3K/Akt 炎症 糖尿病视网膜病变 

分 类 号：R587.2[医药卫生—内分泌] R774.1[医药卫生—内科学]