1.MedicalCollegeofAnkangVocationalandTechnical College;2.Wenzhou Medical University;3.ShaanxiProvicialPeople'sHospital;4.Xi'anJiaotongUniversityHealthScienceCenter
The Natural Science Basic Research Project of Shaanxi Provinc (No.2022JM-571), Science and Technology Development Incubation Fund of Shaanxi Provincial People's Hospital (No.2021YJY-20).
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及免疫荧光检测同源性磷酸酶-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升高，PTEN及炎性因子水平下降，组间比较差异有显著的统计学意义（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。
Aims：To study the protective effect of fenofibrate on diabetic retinal neurodegeneration and observe the expression of miR-26a-5p and its target gene PTEN in the retinal of diabetic mice. Methods：Diabetic mice were induced and 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 expreesion of miR-26a-5p, Western blotting and immunofluorescence were employed to measure the expression of phosphatase and tensin homologue(PTEN) in the retina of diabetic mice. The expression level of NF-κB (nuclear factor-κB), IL-1β (interleukin-1β) and the morphology of neural tissues were observed were examined in the retina of diabetic mice. Results：When compared with the diabetic mice, fenofibrate significantly attenuated retinal neuronal decrease and neuroretina thinning. While the level of miR-26a-5p was increased and the expression of PTEN and inflammatory factors were significantly decreased in the retina of fenofibrate threated diabetic mice(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.