背景C57BL/6.NOD-Aecl Aee2小鼠是研究人干燥综合征发病机制较理想的动物模型,但其干眼体征、眼表组织的病理学特点尚不清楚。目的观察C57BL/6.NOD-Aeel Aee2干燥综合征模型小鼠眼表组织的病理学变化,明确其是否能够自发地产生干眼。方法实验分为模型组(45只C57BL/6.NOD-Aeel Aee2干燥综合征模型小鼠)和对照组(45只C57BL/6J小鼠)。在两组小鼠第4、8、12、16、20周龄时依次进行空腹血糖检测、泪液分泌试验(sIt)、角膜和结膜丽丝胺绿染色及评分;5个时间点每组各取5只小鼠处死、取材,进行中央角膜上皮厚度测量、结膜杯状细胞计数,泪腺淋巴细胞浸润评估及角膜上皮细胞表面微绒毛观察。结果第4周龄时,两种小鼠均未见明显干眼体征。随着周龄的增加,C57BL/6.NOD-Aecl Aec2小鼠泪液分泌逐渐减少,第8、12、16、20周龄酚红棉线长度依次为(2.7±O.9)、(2.5±0.8)、(1.8±0.6)、(1.9±0.1)mm,均明显短于同龄的C57BL/6J小鼠,差异均有统计学意义(P〈0.01);C57BL/6.NOD-Aecl Aee2小鼠角膜结膜丽丝胺绿染色评分值随周龄增加明显升高,12、16和20周龄时其角膜结膜丽丝胺绿染色评分值均明显高于同龄C57BL/6J小鼠,差异均有统计学意义(P〈0.01)。C57BL/6.NOD-Aecl Aee2小鼠角膜上皮厚度值随周龄的增加逐渐降低,8、12、16、20周龄小鼠中央角膜上皮厚度值均明显低于同龄C57BL/6J小鼠,差异均有统计学意义(P〈0.01)。C57BL/6.NOD-AeelAee2小鼠结膜杯状细胞数随周龄的增加逐渐减少,8、12、16、20周龄时分别为(8.2±2.4)、(6.2±2.1)、(6.1±2.2)、(4.1±2.0)个,均明显少于同龄C57BL/6J小鼠,差异均有统计学意义(P〈0.01)。泪腺淋巴细胞浸润及腺体破坏加重;扫描电子显微镜观察显示,角膜上皮细胞脱落增多,
Background C57BL/6. NOD-AeclAec2 mouse is considered to be an idea model for the study of the pathogenesis of Sjtigren syndrome,but the cause of dry eye in these mice is unclear. Objective This study was to investigate the histopathological change of the ocular surfaces of C57BL/6. NOD-AeclAec2 mice, and to determine whether dry eye is developed spontaneously in these mice. Methods Forty-five clean C57BL/6. NOD- AeclAee2 mice were used as the experiment group and forty-five C57BL/6J mice( both male and female)were used as the control group in this study. Detection of fasting blood-glucose, Schirmer' s test I (S I t) , lissamine green staining and scoring of the corneal and conjunctival epithelium in the mice were performed at the age of 4,8,12,16 and 20 weeks. Five mice from each group were sacrificed and their corneas were obtained to measure the central corneal epithelium thickness and to count the number of conjunctival goblet cells. In addition,lymphocyte infiltration in the lacrimal gland of the mice was examined with hematoxylin-eosin staining. The ultrastructure of the corneal epithelial cells and microvilli were assessed by scanning electron microscopy. The use and care of the mice were approved by the Experimental Animal Care Committee of the Third Military Medical University. Results No sign of dry eye wasseen in both the 4-week-old C57BL/6. NOD-AeclAec2 mice and 4-week-old C57BL/6J mice. The S I t values in 8- week-old,12-week-old,16-week-old and 20 week-old mice from the experiment group were( 2.7±0. 9 )mm, (2.5 ± 0.8 )mm, (1.8±0.6)mm and( 1.9±0. 1 )mm, respectively, showing a significant reduction in comparison with those of the control mice of the same age( all P〈0.01 ). The amount of lissamine green staining in the C57BL/6. NOD- AeclAec2 mice gradually increased with age, showing elevated scores in 12-week-old, 16-week-old and 20-week-old mice in the experiment group (all P〈0.01 ). The central corneal epithelium thicknesses were (20. 18 ± 3.75 ) μm, ?