摘要
目的探讨抑制糖原合成酶激酶-3β(GSK-3β)对糖尿病小鼠视网膜神经细胞损伤的影响,并探讨其潜在机制。方法前瞻性研究。健康雄性C57BL/6J小鼠,采用链脲佐菌素(STZ)腹腔注射构建糖尿病模型,视网膜HE染色及超微结构观察视网膜神经变性及神经细胞中线粒体损伤情况,Realtime PCR及免疫荧光检测视网膜中GSK-3βmRNA及蛋白的表达,并ELISA法检测视网膜中IL-6及IL-1β的水平变化。糖尿病小鼠玻璃体腔注射GSK-3β拮抗剂,观察其下游炎性因子的表达及视网膜神经元线粒体损伤情况。结果与糖尿病相比,GSK-3β阻断组糖尿病小鼠视网膜神经纤维层萎缩及神经元线粒体凋亡明显减轻,视网膜中炎性因子水平下降,组间比较差异有统计学意义(P<0.05)。结论阻断GSK-3β通过抑制炎症反应,减少神经元线粒体损伤,发挥糖尿病视网膜神经保护作用。
Objective To study the effect of inhibition of GSK-3βactivity on diabetic retinal neurodegeneration and to explore its mechanism.Methods A prospective study.Healthy male C57BL/6J were used to construct a diabetic mouse model by streptozocin(STZ)intraperitoneal injection.Hematoxylin and eosin(HE)and transmission electron microscopy were used to observe retinal neurons and mitochondrion injury.The mRNA and protein expression of glycogen synthase kinase-3β(GSK-3β)were examined by real-time polymerase chain reaction(PCR)and immunofluorescence in diabetic retinal tissue.The levels of interleukin-6(IL-6)and IL-1βin the retina were observed by enzyme-linked immunosorbent assay(ELISA).Diabetic mice were further subjected to intravitreal injection of GSK-3βinhibitor to observe the expression of downstream inflammatory factors and mitochondrial damage of retinal neurons.Results Compared with diabetes,the retinal nerve fiber layer atrophy and neurons mitochondrial damage of the GSK-3βgroup were significantly reduced,and the levels of inflammatory factors declined.The difference between groups was significant(P<0.05).Conclusions Inhibition of GSK-3βactivity reduces the level of inflammatory factors,alleviates neuronal mitochondrial damage and exerts diabetic retinal neuroprotective effects.
作者
唐德荣
石蕊
张阳炼
姜明玖
Tang Derong;Shi Rui;Zhang YangLian;Jiang MingJiu(Department of Ophthalmology,Medical College of Ankang Vocational and Technical College(Ankang Central Hospital),Ankang 725000,China;Department of Ophthalmology,Shanxi Provincial People’s Hospital,Xi’an 710068,China;Department of Ophthalmology,Baihe County People's Hospital,Ankang 725000,China;Department of Ophthalmology,Ankang City high-tech Hospital,Ankang 725000,China)
出处
《临床眼科杂志》
2024年第4期350-354,共5页
Journal of Clinical Ophthalmology
基金
陕西省自然科学基础研究计划项目(2022JM571)
陕西省人民医院科技发展孵化基金资助项目(2021YJY20)。
关键词
糖尿病视网膜神经损伤
GSK-3Β
炎症
线粒体损伤
Diabetic retinal neurodegeneration
Glycogen synthase kinase-3β
Inflammation
Mitochondrial damage
