目的:探讨维生素D3(VD3)联合rhG-CSF对实验性糖尿病(diabetes mellitus,DM)小鼠眼部结构损伤的作用。方法:健康C57BL/6小鼠22只,体质量20~25g,随机分为联合治疗实验组、DM对照组,并设健康对照。用20g/L链脲佐菌素(streptozotocin,STZ)ip,制备实验性DM模型,实验组小鼠制模后14d行VD35mg/kg ip,1次/wk;制模后28d行20μg/kg rhG-CSF sc,1次/d,连续注射5d。两组每周进行血糖监测和眼底镜观察。每周各组随机摘取3只眼球,常规病理制片后镜下观察眼球各部分结构,利用病理图像分析系统测量中央角膜、视乳头旁1PD处脉络膜厚度和视网膜神经上皮层的厚度。结果:DM小鼠7d角膜中央出现明显水肿,21d达高峰后逐渐减轻,经联合治疗后小鼠角膜厚度一直呈现减少趋势,水肿情况比DM对照组有明显缓解,接近健康小鼠平均值。DM小鼠7d角膜上皮厚度明显增加,21d达高峰后逐渐下降,到35d后DM对照组角膜上皮厚度持续下降,萎缩明显,联合治疗组的角膜上皮厚度接近正常(P>0.05)。DM小鼠7d脉络膜厚度降低,开始萎缩,逐渐加剧,联合治疗组在28d后脉络膜厚度明显增加,到49d时与正常小鼠无差异,两组DM小鼠的视网膜神经上皮层厚度均呈逐渐下降趋势,联合治疗组的下降趋势略缓和。结论:VD3联合rhG-CSF治疗能有效缓解小鼠DM角膜水肿,改善角膜上皮萎缩,有效缓解并改善脉络膜萎缩,对视网膜神经上皮层萎缩也有一定的保护作用。

·AIM:To study the protective effect of vitamin D3(VD3)combined with recombinant human granulocyte colony-stimulating factor(rhG-CSF)on ocular structure of experimental diabetic mice.METHODS:Of 22 mice(C57/BL6 rats weighing 20-25g),3 healthy rats were chosen for blank control after glucose analysis.The others were diabetic models produced by 20g/L streptozotocin(STZ)injection(175mg/kg intraperitoneally in citrate buffer)after fasting for 15 hours.Blood was obtained from a tail vein to make glucose analysis 3 times in the third day after STZ injection(blood glucose concentration>16.7mmol/L as diabetic model).They were randomly distributed into two groups:experimental group(E group),control group(C group).In 14th day after STZ injection,E group animals were treated with VD3 5mg/kg intraperitoneally once a week;In 28th day after STZ injection,with hypodermic injection of rhG-CSF 20μg/kg per days for 5 consecutive days.At the 7th,14th,21st,28th,35th,42nd,49th day,blood sugar monitoring,direct ophthalmoscope examination and thickness measurement were taken by pathologic analyzing software.Data were processed by SPSS 16.0.RESULTS:Corneal edema of C group lasted from 1st week to 7th week.After combined treatment,corneal edema turned better(F=1668.887,P=0.00).Two groups had significant difference at different time(F=546.835,P=0.00).There were significant interaction effects between the time and group factors(F=163.566,P=0.00).At 5th week,corneal epithelium atrophy of C group was significant(F=96.914,P=0.00),E group was near normal(P>0.05).Choroid membrane atrophy of C group lasted from 1st week to 7th week.E group had protective effects on choroid membrane(F=1579.832,P=0.00).Both groups had atrophy of the retina,but E group was better than C group(F=531.239,P=0.00).CONCLUSION:VD3 combined with rhG-CSF has significant protective effect on ocular structure of experimental diabetic mouse.

R587.1

中国广东省卫生厅科研基金资助项目（No.A2008614）