非诺贝特对糖尿病小鼠视网膜神经组织中miR-26a-5p/PTEN表达的影响  

Effect of fenofibrate on the expression of miR-26a-5p/PTEN in retinal neurons of diabetic mice

作　　者：唐德荣 杨雨雯[3] 石蕊 刘丹丹[4] 林蓉 Tang Derong;Yang Yuwen;Shi Rui;Liu Dandan;Lin Rong(Medical College of Ankang Vocational and Technical College,Ankang 725000,Shaanxi Province,China;Department of Ophthalmology,Ankang Central Hospital,Ankang 725000,Shaanxi Province,China;State Key Laboratory of Ophthalmology,Optometry and Visual Science,Wenzhou Medical University,Wenzhou 325035,Zhejiang Province,China;Department of Ophthalmology,Shaanxi Provincial People's Hospital,Xi'an 710068,Shaanxi Province,China;School of Basic Medical Sciences,Xi'an Jiaotong University,Xi'an 710061,Shaanxi Province,China)

机构地区：[1]安康职业技术学院医学院,中国陕西省安康市725000 [2]中国陕西省安康市中心医院眼科,725000 [3]温州医科大学眼科实验室,中国浙江省温州市325035 [4]陕西省人民医院眼科,中国陕西省西安市710068 [5]西安交通大学基础医学院,中国陕西省西安市710061

出　　处：《国际眼科杂志》2024年第1期24-29,共6页International Eye Science

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:研究非诺贝特对糖尿病小鼠视网膜神经损伤的保护作用并观察其对miR-26a-5p及其靶基因PTEN的影响。方法:构建糖尿病小鼠模型,并进行非诺贝特灌胃,H&E及透射电镜观察视网膜神经损伤情况,Real-time PCR检测视网膜组织中miR-26a-5p的表达,Western blotting检测同源性磷酸酶-张力蛋白(PTEN)在视网膜组织中的表达,并观察NF-κB及IL-1β的水平及视网膜神经上皮的结构变化。结果:与糖尿病组相比,非诺贝特治疗组糖尿病小鼠视网膜神经节细胞损伤及神经纤维层萎缩明显减轻,视网膜中miR-26a-5p表达升高,PTEN mRNA和蛋白表达下降,炎性介质NF-κB及IL-1βmRNA表达水平下降(P<0.05)。结论:非诺贝特通过上调miR-26a-5p抑制PTEN的表达,降低炎症因子水平,减轻视网膜细胞损伤,发挥糖尿病视网膜神经保护作用。AIM:To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe its effect on miR-26a-5p and its target gene PTEN in the retinal of diabetic mice.METHODS:Diabetic mice models were established and they were gavaged by fenofibrate.H&E staining and transmission electron microscopy were used to observe the impairments of retinal neurons.Real-time PCR was used to examine the expression of miR-26a-5p,and Western blotting was employed to measure the expression of phosphatase and tensin homologue(PTEN)in the retina of diabetic mice.The expression level of nuclear factor-κB(NF-κB),interleukin-1β(IL-1β)and the morphology of neural tissues were observed.RESULTS:When compared with the diabetic mice,fenofibrate significantly attenuated the damage to retinal ganglion cells and the atrophy of retinal nerve fiber layer.While the level of miR-26a-5p was increased and the levels of PTEN and inflammatory mediators were significantly decreased in the retina of fenofibrate treated diabetic mice,with significant statistical significance(P<0.05).CONCLUSIONS:Fenofibrate protects against diabetic retinal neurodegeneration by upregulating miR-26a-5p and inhibiting PTEN,attenuating the inflammatory response and alleviating retinal cell injury.

关 键 词：糖尿病视网膜神经损伤 miR-26a-5p 同源性磷酸酶-张力蛋白(PTEN) 炎症 非诺贝特 

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