叶酸联合地西他滨对糖尿病小鼠的治疗作用
Therapeutic effect of folic acid combined with decitabine on diabetic mice.
作者信息
Du Gang, Yan Yong, Gao Jun-Feng, Guo Chun-Yan, Shen Xiao, Lei Xun-Wen
机构信息
The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China.
Huining Second People's Hospital, Baiyin 730700, Gansu Province, China.
出版信息
Int J Ophthalmol. 2023 Nov 18;16(11):1766-1772. doi: 10.18240/ijo.2023.11.05. eCollection 2023.
AIM
To evaluate the therapeutic effect of folic acid combined with decitabine on diabetic mice.
METHODS
The diabetic model of mice were randomly divided into model group, folic acid group, decitabine group, folic acid combined with decitabine group, and C57 mice as normal control group. The density of retinal blood vessels and retinal thickness were detected by fundus photography and optical coherence tomography, respectively. Pathological changes of retina were observed by hematoxylin-eosin (HE) staining. The homocysteine (Hcy) in serum was detected by enzyme linked immunosorbent assay (ELISA). TdT-mediated dUTP nick-end labeling (TUNEL) was used to detect apoptosis in retinal tissue. Evans blue dye was used to detect the permeability of retinal blood vessels. The platelet endothelial cell adhesion molecule-1 (CD31) and vascular endothelial growth factor receptor (VEGFR) protein were detected by Western blot. The 3-nitrotyrosine (3-NT) and 4-hydroxynonanine (4-HNE) were detected by immunohistochemistry.
RESULTS
The density of retinal blood vessels, retinal thickness, retinal vascular permeability and the proportion of apoptotic cells of retinal tissue in the model group increased significantly than control group (<0.05). The Hcy in serum and the levels of CD31, VEGFR, 3-NT, and 4-HNE in retinal tissue increased significantly in the model group (<0.01). Folic acid and decitabine both reversed these changes significantly, and the combination of the folic acid and decitabine worked best.
CONCLUSION
The combination of folic acid and decitabine has a more significant protective effect on the retina in diabetic mice.
目的
评估叶酸联合地西他滨对糖尿病小鼠的治疗效果。
方法
将糖尿病小鼠模型随机分为模型组、叶酸组、地西他滨组、叶酸联合地西他滨组，将C57小鼠作为正常对照组。分别通过眼底照相和光学相干断层扫描检测视网膜血管密度和视网膜厚度。采用苏木精-伊红（HE）染色观察视网膜的病理变化。采用酶联免疫吸附测定（ELISA）法检测血清中的同型半胱氨酸（Hcy）。采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法（TUNEL）检测视网膜组织中的细胞凋亡。采用伊文思蓝染料检测视网膜血管的通透性。采用蛋白质印迹法检测血小板内皮细胞黏附分子-1（CD31）和血管内皮生长因子受体（VEGFR）蛋白。采用免疫组织化学法检测3-硝基酪氨酸（3-NT）和4-羟基壬烯酸（4-HNE）。
结果
模型组视网膜血管密度、视网膜厚度、视网膜血管通透性及视网膜组织凋亡细胞比例均较对照组显著增加（<0.05）。模型组血清Hcy及视网膜组织中CD31、VEGFR、3-NT和4-HNE水平均显著升高（<0.01）。叶酸和地西他滨均能显著逆转这些变化，且叶酸与地西他滨联合使用效果最佳。
结论
叶酸联合地西他滨对糖尿病小鼠视网膜具有更显著的保护作用。
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