Alves M, Calegari V C, Cunha D A, Saad M J A, Velloso L A, Rocha E M
Laboratory of Clinical Physiopathology, Department of Clinical Medicine, School of Medicine, State University of Campinas (UNICAMP), Campinas, Brazil.
Diabetologia. 2005 Dec;48(12):2675-81. doi: 10.1007/s00125-005-0010-9. Epub 2005 Nov 8.
AIMS/HYPOTHESIS: To assess the involvement of the AGE-specific receptor (AGER, also known as RAGE) axis and nuclear factor kappa-B (NFKB, also known as NF-kappaB) activation in the development of lacrimal gland and tear film dysfunction in diabetes, the present study evaluated: (1) lacrimal gland and tear film alterations in diabetic rats; and (2) the expression of AGE, AGER and NFKB in ocular tissues of normoglycaemic and diabetic rats.
Diabetes was induced in male Wistar rats with intravenous streptozotocin. Tear secretion parameters were measured and NFKB expression was evaluated in lacrimal glands of control and diabetic rats by western blot. Immunohistochemistry with confocal microscopy was used to assess AGE, AGER and NFKB expression in lacrimal glands of both groups.
Lacrimal gland weight and tear film volume were lower in diabetic than in control rats (p=0.01 and 0.02, respectively). IL1B and TNF concentrations in tears were higher in diabetic than in control rats (p=0.007 and 0.02, respectively). NFKB protein was identified in rat cornea, conjunctiva and lacrimal glands. AGE, AGER and NFKB expression were greater in lacrimal glands of diabetic than in those of control rats.
CONCLUSIONS/INTERPRETATION: Diabetes induces significant alterations in rat lacrimal gland structure and secretion. The higher expression of AGE, AGER and NFKB in lacrimal glands of diabetic rats suggests that these factors are involved in signalling and in subsequent inflammatory alterations related to dry eye in diabetes mellitus.
目的/假设：为了评估特定年龄受体（AGER，也称为RAGE）轴和核因子κB（NFKB，也称为NF-κB）激活在糖尿病患者泪腺和泪膜功能障碍发展中的作用，本研究评估了：（1）糖尿病大鼠的泪腺和泪膜改变；以及（2）血糖正常和糖尿病大鼠眼组织中AGE、AGER和NFKB的表达。
用静脉注射链脲佐菌素诱导雄性Wistar大鼠患糖尿病。测量泪液分泌参数，并通过蛋白质印迹法评估对照大鼠和糖尿病大鼠泪腺中NFKB的表达。采用共聚焦显微镜免疫组织化学法评估两组泪腺中AGE、AGER和NFKB的表达。
糖尿病大鼠的泪腺重量和泪膜体积低于对照大鼠（分别为p = 0.01和0.02）。糖尿病大鼠泪液中的IL1B和TNF浓度高于对照大鼠（分别为p = 0.007和0.02）。在大鼠角膜、结膜和泪腺中鉴定出NFKB蛋白。糖尿病大鼠泪腺中AGE、AGER和NFKB的表达高于对照大鼠。
结论/解读：糖尿病可导致大鼠泪腺结构和分泌发生显著改变。糖尿病大鼠泪腺中AGE、AGER和NFKB的高表达表明这些因素参与了与糖尿病性干眼相关的信号传导和随后的炎症改变。
