PI3K/AKT/mTOR通路
神经保护
内分泌学
免疫印迹
生理盐水
兴奋毒性
内科学
多奈哌齐
链脲佐菌素
细胞凋亡
半胱氨酸蛋白酶3
药理学
谷氨酸受体
医学
化学
糖尿病
受体
程序性细胞死亡
生物化学
基因
疾病
痴呆
作者
Sawsan A. Zaitone,Reem Alshaman,Abdullah Alattar,Nehal M. Elsherbiny,Noha M. Abogresha,Mohamed K. El-Kherbetawy,Abdelhakeem Elaskary,Abdullah A. Hashish,Laila Ahmed Rashed,Eman Ahmed
出处
期刊:Life Sciences
[Elsevier]
日期:2020-12-01
卷期号:262: 118467-118467
被引量:9
标识
DOI:10.1016/j.lfs.2020.118467
摘要
Donepezil (DNPZ) has shown neuroprotective effect in many disorders. The current study tested the putative retinoprotection provided by donepezil in mouse diabetic retinopathy. Swiss albino mice were allocated to, 1] saline control, 2] diabetic, 3&4] diabetic+DNPZ (1 or 4 mg/kg). After induction of diabetes, mice were maintained for 8 weeks then DNPZ therapy was launched for 28 days. Retinas were isolated and used for histopathology and immunohistochemistry for caspase 3 and the anti-apoptotic protein, B-cell lymphoma 2 (BCl2). Retinas were examined for glutamate, acetylcholine and oxidation markers. Western blot analysis measured inflammatory cytokines, N-methyl-d-aspartate receptors (NMDARs), phosphorylated and total phosphatidylinositol-3 kinase and mTOR, BCl2 and cleaved caspase 3. Significant histopathological changes and decreased thickness were found in diabetic retinas (125.52 ± 2.85 vs. 157.15 ± 7.55 in the saline group). In addition, retinal glutamate (2.39-fold), inflammatory cytokines and NMDARs proteins (4.9-fold) were higher in the diabetic retinas. Western blot analysis revealed low ratio of phosphorylated/total PI3K (0.21 ± 0.043 vs. 1 ± 0.005) and mTOR (0.18 ± 0.04 vs. 1 ± 0.005), low BCl2 (0.28 ± 0.06 vs. 1 ± 0.005) and upregulated cleaved caspase 3 (5.18 ± 1.27 vs. 1 ± 0.05 in the saline group) versus the saline control. DNPZ ameliorated the histopathologic manifestations and to prevent the decrease in retinal thickness. DNPZ (4 mg/kg) improved phosphorylation of PI3K (0.76 ± 0.12 vs. 0.21 ± 0.04) and mTOR (0.59 ± 0.09 vs. 0.18 ± 0.04) and increased BCl2 (0.75 ± 0.08 vs. 0.28 ± 0.06) versus the diabetic control group. This study explained the retinoprotective effect of DNPZ in mouse diabetic retinopathy and highlighted that mitigation of excitotoxicity, improving phosphorylation of PI3K/mTOR and increasing BCl2 contribute to this effect.
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