抑制GSK-3β活性对糖尿病小鼠视网膜神经细胞损伤的影响
Effect of inhibition of GSK-3βactivity on diabetic retinal neurodegeneration
唐德荣 1石蕊 2张阳炼 3姜明玖4
作者信息
- 1. 725000 安康,安康市中心医院
- 2. 710068 西安,陕西省人民医院
- 3. 725000 安康,白河县人民医院
- 4. 725000 安康市高新医院
- 折叠
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,Real-time PCR及免疫荧光检测视网膜中GSK-3β mRNA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.
Abstract
Objective To study the effect of inhibition of GSK-3β activity 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 mi-croscopy were used to observe retinal neurons and mitochondrion injury.The mRNA and protein expression of glycogen syn-thase kinase-3β(GSK-3β)were examined by real-time polymerase chain reaction(PCR)and immunofluorescence in dia-betic retinal tissue.The levels of interleukin-6(IL-6)and IL-1β in the retina were observed by enzyme-linked immunosor-bent assay(ELISA).Diabetic mice were further subjected to intravitreal injection of GSK-3β inhibitor to observe the ex-pression of downstream inflammatory factors and mitochondrial damage of retinal neurons.Results Compared with diabe-tes,the retinal nerve fiber layer atrophy and neurons mitochondrial damage of the GSK-3β group were significantly re-duced,and the levels of inflammatory factors declined.The difference between groups was significant(P<0.05).Conclu-sions Inhibition of GSK-3β activity reduces the level of inflammatory factors,alleviates neuronal mitochondrial damage and exerts diabetic retinal neuroprotective effects.
关键词
糖尿病视网膜神经损伤/GSK-3β/炎症/线粒体损伤Key words
Diabetic retinal neurodegeneration/Glycogen synthase kinase-3β/Inflammation/Mitochondrial dam-age引用本文复制引用
基金项目
陕西省自然科学基础研究计划(2022JM-571)
陕西省人民医院科技发展孵化基金(2021YJY-20)
出版年
2024
国家科技期刊平台
NSTL
万方数据