基于氧化应激探索白藜芦醇抑制糖尿病视网膜病变的分子机制

Exploration into Molecular Mechanism of Resveratrol Inhibiting Diabetic Retinopathy Based on Oxidative Stress

目的:探索白藜芦醇对糖尿病视网膜病变(diabetic retinopathy,DR)的抑制作用及其机制。方法:将db/db小鼠20只随机分为模型组和白藜芦醇组,另设10只C57BL/KsJ小鼠作为对照组,其中白藜芦醇组灌胃50 mg/kg白藜芦醇,每天1次,连续60天,对照组和模型组灌胃相同体积生理盐水,每天1次,连续60天。定期观察并记录各组小鼠运动、精神状态、体质量及空腹血糖变化情况;2个月后麻醉各组小鼠,摘取眼球、分离视网膜,HE染色观察视网膜病理变化情况;采用Western bloting方法检测视网膜中Bax、B淋巴细胞瘤2(B-cell lymphoma-2,Bcl-2)、血红素加氧酶(heme oxygenase 1,HO-1)、γ-谷氨酰半胱氨酸合成酶(γ-glutamylcysteine synthetase,γ-GCS)蛋白变化情况;采用生化试剂盒检测视网膜中超氧化物歧化酶(superoxide dismutase,SOD)、8羟基脱氧乌苷(8-hydroxy-2deoxyguanosine,8-OHdG)、丙二醛(malonaldehyde,MDA)水平。结果:白藜芦醇可延缓2型糖尿病小鼠体质量增加,降低空腹血糖,提高运动能力和精神状态,缓解视网膜病变,降低糖尿病视网膜组织细胞凋亡,提高糖尿病视网膜组织中HO-1、γ-GCS、T-SOD蛋白,降低8-OHdG、MDA水平。结论:白藜芦醇可通过降糖作用缓解DR的发生发展,并通过激活视网膜组织中抗氧化酶系统提高抗氧化能力,降低视网膜中活性氧水平,从而抑制DR的发生发展。

Objective:To explore inhibitory effects of resveratrol on diabetic retinopathy(DR)and its mechanism.Methods:All 20 mice were randomized into the model group and resveratrol group,and another ten mice were chosen as the control group,the resveratrol group were drenched with resveratrol,50 mg/kg,once each day,for 60 days consecutively,the control group and the model group accepted intragastric administration of equivalent volume of normal saline,once each day,for 60 days consecutively.To observe and record the changes of motion state,mental state,body mass and fasting blood glucose(FBG)of the mice in different groups regularly;the pathological changes of retina were observed through HE staining when the eyeballs of the mice were removed after the anaesthesia in two months;the changes ofγ-GCS protein,HO-1,Bcl-2 and Bax in the retina were detected using Western bloting method;the levels of SOD,8-OHdG and MDA in the retina were measured using biochemical kit.Results:Resveratrol could delay the increase of body mass of the mice with type two diabetes mellitus(T2DM),lower FBG,improve motion state and mental state,prolong retinopathy of T2DM mice,decrease the apoptosis of diabetic retina cells,raise HO-1,γ-GCS and T-SOD protein in diabetic retinal tissue and reduce the levels of 8-OHdG and MDA.Conclusion:Resveratrol could relieve the incidence and the development of DR through self glucose-lowering effects,raise antioxidant capacity via activating antioxidant enzyme system in the retinal tissue,lowering the levels of active oxygen,therefore to restrain the incidence and the development of DR.