维生素D_3对实验性糖尿病小鼠眼部结构的保护作用

背景研究证实，维生素D，通过其生物活化形式1，25-（OH），D，与维生素D受体结合，从而发挥抗炎、免疫调节、神经保护作用。此外，维生素D，可以增强胰岛素的敏感性及促进胰岛素的分泌，控制高血糖症，减轻角膜水肿。目的研究维生素D，对缓解实验性糖尿病小鼠眼部结构损伤的作用。方法健康SPF级C57BL／6小鼠22只（体质量20-25g），应用随机数字表法随机选取8只小鼠为维生素D，组，另取11只小鼠为糖尿病对照组，并取3只小鼠为正常对照组。利用腹腔注射质量分数2％链脲佐菌素（STZ）法制备实验性糖尿病模型，造模后2周维生素D，组小鼠行腹腔注射维生素D，5mg／kg，每周注射1次，共5次。各组每周进行血糖监测、直接检眼镜观察。各组每周随机摘取3只眼球，常规病理切片后于光学显微镜下观察眼球各部分结构，利用病理分析软件测量中央角膜、视盘旁1个视盘直径（DD）处脉络膜厚度及视网膜神经上皮层的厚度。结果糖尿病对照组小鼠造模后第1周角膜开始出现水肿，角膜平均厚度为（339．14＋11．13）μm，以后水肿持续但逐渐减轻（F=382．446，P=0．000）。维生素D，干预后水肿情况明显缓解，角膜厚度明显变薄（P〈0．05）。两组糖尿病小鼠第5周角膜上皮均开始萎缩（P〈0．05），糖尿病对照组至第7周萎缩情况更加严重，而维生素D，组小鼠至第7周萎缩已明显减轻（P=0．002）。糖尿病小鼠脉络膜自第1周开始萎缩（P=0．010），并随时间延长萎缩加重（F=437．411，P=0．000）。维生素D，干预后，第4周脉络膜萎缩趋势明显减缓，且用药后从第3周开始维生素D，组脉络膜厚度均大于糖尿病对照组（P〈0．05），糖尿病小鼠自第1周开始视网膜神经上皮层即可见明显的凹凸不平，轻度水肿（P=0．000），随时间延长，糖尿病造成的视网膜神经上皮层萎缩加重（F=91．859，P=0．000）。维生素D，组视网膜神经上皮层萎缩情况无明显改变。结论维生素D，对实验性糖尿病小鼠角膜及脉络膜有保护作用，但其对已萎缩的视网膜并无明显的修复作用。

Protective effect of vitamin D_3 on ocular structure in diabetic rat

Background Research demonstrated that vitamin D3 mediated by its receptor has the potent nonclassical effects, including immunomodulatory, antiinflammatory, and neuroprotective properties, and it can enhance the secretion and sensitivity of insulin and therefore downregulate hyperglycemia and attenuate the corneal edema. Objective The present study was to investigate the protective effect of vitamin D3on ocular structure in experimental diabetic rat. Methods Twentytwo healthy SPF C57BL/6 rats were randomly divided into vitamine D3 group （8 rabbits） ,diabetic control group（ 11 rabbits） and normal control group（3 rabbits）. 2% streptozotoein（STZ,175 mg/kg） was intraperitoneally injected to create the diabetic models in the rats of the vitamine D3 group and diabetic control group. Blood glucose was examined for 3 times in the third day after STZ injection, and the rats with the blood glucose concentration 〉16.7 mmol/L was identified as the successful diabetic models. After modeling, the rat tail blood was collected for the monitoring of blood glucose. Two weeks after modeling,vitamine D3 was intraperitoneally injected in each week for 5 times. The fundus was examined using direct ophtalmoseope,and the eyeballs were obtained under the excessive anesthesia for the measurement of thickness of the central cornea, retina and choroids by histopathologieal examination once a week for 7 weeks after administration of vitamin D3. The administration of the animals complied with the Statement of ARVO. Results The corneal edema appeared with the corneal thickness of （339. 14_＋11.13）μm in the first week and gradually attenuated with time elapse after modeling in the diabetic group （ F = 382. 446, P = 0. 000）. The corneal thickness values were significantly decreased from the second week through the seventh weekin the vitamin D_3 group compared with diabetic control group（P〈0.05）. The atrophy of the corneal epithelium was found from lhe fifth week to the sevenlh week in diabetic control group, but that in vitamin D3 group was slight （ P〈0.05 ）. The gradually lhinning of the ehoroids was seen fl＇om the first week to the seventh week in the diabetic control group （ F = 437.411 , P = 0. 000 ） , however, the thickness values in the vilamin 1）3 group were significantly increased in comparison with the diabetic control group in various time points（ P〈0.05 ）. The retina thiekness was gradually reduced during the sew~n-week duration in the diahetie control group （ F = 91. 859, P = 0. 000） , but no signifieant change was identified in retina thickness in the vitamin Ds group（P〉0.05）. Conclusions Vitamin Ds has prevent and therapeutic effeels on experimental diabetie oeuh〉pathy.