摘要
目的:探究不同剂量熊果酸(UA)干预糖尿病小鼠视网膜病变的作用及机制。方法:选取雄性健康C57BL/6小鼠60只,其中50只按50 mg/kg的剂量一次性往小鼠尾静脉注射新鲜配置的四氯嘧啶生理盐水溶液构建小鼠糖尿病视网膜病变模型,随机分为5组,每组10只,分别为模型组、阳性对照组(小鼠玻璃体注射3μL 40 mg/m L的曲安奈德),低剂量UA干扰组(小鼠玻璃体注射3μL剂量为0.5μg/μL的UA)、中剂量UA干扰组(小鼠玻璃体注射3μL剂量为1.0μg/μL的UA),高剂量UA干扰组(小鼠玻璃体注射3μL剂量为2.0μg/μL的UA),余下10只小鼠作为正常对照组。观察各组小鼠对胰岛素敏感性、视网膜内糖代谢情况、小鼠视网膜神经节细胞(RGCs)凋亡情况,比较各组小鼠视网膜组织中血管内皮生长因子(VEGF)、环氧化酶-2(COX-2)、基质金属蛋白酶2(MMP-2)蛋白及其mRNA的表达情况。结果:建模后,正常对照组胰岛素抵抗指数(HOMA-IR)、视网膜含糖量、葡萄糖转运体-1(GLUT-1)与葡萄糖转运体-3(GLUT-3)含量、RGCs凋亡率、视网膜组织中VEGF、COX-2、MMP-2蛋白及其mRNA的表达量低于模型组(P<0.05);经干扰后,阳性对照组、不同剂量UA干扰组HOMA-IR、视网膜含糖量、GLUT-1、GLUT-3的含量、RGCs凋亡率、视网膜组织中VEGF、COX-2、MMP-2蛋白及其mRNA的表达量低于模型组(P<0.05),且随UA干扰剂量的升高而降低(P<0.05)。结论:UA能够降低HOMA-IR和视网膜糖代谢能力,抑制RGCs的凋亡,对VEGF、COX-2、MMP-2蛋白及其mRNA的表达具有一定的抑制作用,高剂量UA对糖尿病小鼠视网膜病预防治疗效果较好。
Objective: To investigate the effect and mechanism of different dose of ursolic acid on retinopathy in diabetic mice.Methods: 60 male healthy C57 BL/6 mice were selected, an among them, 50 mice were injected with a dose of 50 mg/kg to the tail vein was injected the fresh-configured four-chlorofluorocarbon saline solution of mice to construct a diabetic retinopathy model, randomly divided into 5 groups, 10 mice in each group, they were model group, positive control group(Mice were vitreous injected with 3 μL 40 mg/ml of triamcinolone), low dose UA interference group(Mice were vitreous injected with 3 μL 0.5 μg/μL of UA), mid dose UA interference group(Mice were vitreous injected with 3 μL 1.0 μg/μL of UA), high dose UA interference group(Mice were vitreous injected with 3 μL 2.0 μg/μL of UA), the remaining 10 mice as normal control group. The insulin sensitivity, glucose metabolism in retina and apoptosis of retinal ganglial cells(RGCs) were observed. The expressions of vascular endothelial growth factor(VEGF),cyclooxygenase-2(COX-2) and matrix metalloproteinase-2(MMP-2) and mRNA in retinal tissues of mice in each group were compared.Results: After modeling, insulin resistance index(HOMA-IR), retinal glucose content, glucose transporter-1(GLUT-1) and glucose transporter-3(GLUT-3) content, apoptosis rate of RGCs, expression levels of VEGF protein, COX-2 protein, MMP-2 protein and mRNA of retinal tissues in the normal control group were lower than those in the model group(P<0.05). After interference, HOMA-IR, retinal sugar content, GLUT-1 and GLUT-3 content, apoptosis rate of RGCs, expression levels of VEGF protein, COX-2 protein, MMP-2 protein and mRNA of retinal tissues in positive control group, different dose of UA interference group were lower than those in model group(P<0.05), and decreased with the increase of UA interference dose(P<0.05). Conclusion: UA can reduce HOMA-IR and retinal glucose metabolism, inhibit the apoptosis of RGCs, inhibit the expression of VEGF, COX-2, MMP-2 protein and mRNA, High dose of UA has a good effect on the prevention and treatment of retinopathy in diabetic mice.
作者
闫利锋
李传旭
周瑾
郭梦翔
黄业贤
项道满
YAN Li-feng;LI Chuan-xu;ZHOU Jin;GUO Meng-xiang;HUANG Ye-xian;XIANG Dao-man(Department of Ophthalmology,Guangzhou Women and Children Medical Center,Guangzhou,Guangdong,510623,China)
出处
《现代生物医学进展》
CAS
2020年第5期838-842,共5页
Progress in Modern Biomedicine
基金
广东省医学科研基金项目(B2018135)。
作者简介
闫利锋(1973-),女,博士,副主任医师,研究方向:视网膜病变,E-mail:yanlifeng197310@163.com;通讯作者:项道满(1964-),男,博士,主任医师,研究方向:小儿眼科疾病,E-mail:xiangdm35@126.com。
