Gül Mehmet, Emre Sinan, Eşrefoğlu Mukaddes, Vard Nigar
Department of Histology and Embryology, Faculty of Medicine, Inonu University, Malatya, Turkey.
Cornea. 2008 Aug;27(7):795-801. doi: 10.1097/ICO.0b013e318169d67c.
This study was designed to investigate the protective effect of aminoguanidine (AG) and melatonin (M) on the cornea in a streptozotocin-induced diabetic rat model.
Twenty-eight Sprague-Dawley rats were used in this study. Animals were divided into 4 groups: control (C), diabetes (D), diabetes + AG (D+AG), and diabetes + M (D+M). Diabetes was induced by 1 intraperitoneal dose of 45 mg/kg of streptozotocin (STZ). In the treatment groups, the D + AG group received AG in their water (1 g/L), and D + M rats were injected with M (10 mg/kg/d) intraperitoneally. One of the groups remained an untreated diabetic group (D group). All animals were euthanized at the end of 8 weeks. After enucleation, eyes were fixed in 10% phosphate-buffered formalin and embedded in paraffin wax. Histochemical stains were applied, and specimens were examined under a light microscope.
After 8 weeks, the rats in the diabetes group had significantly lower body weight and significantly higher blood glucose levels than those of the control, D + AG, and D + M groups. Diabetes resulted in prominent edema in the stroma with interruptions in the subepithelial basement membrane. These alterations were not prominent or were absent in the D + AG and D + M groups. The mean thicknesses of the cornea, corneal epithelium, and stroma were statistically significantly different between the C and D, and D and D + AG and D + M groups (P < 0.05).
Long-term administration of AG and M reduced corneal injury in an STZ-induced diabetic rat model. AG and M may be potential candidates in the treatment of diabetic keratopathies. However, further studies are needed to elucidate the mechanisms of the protective effect of both molecules on diabetic corneal complications.
本研究旨在探讨氨基胍(AG)和褪黑素(M)对链脲佐菌素诱导的糖尿病大鼠模型角膜的保护作用。
本研究使用了28只Sprague-Dawley大鼠。动物被分为4组:对照组(C)、糖尿病组(D)、糖尿病+AG组(D+AG)和糖尿病+M组(D+M)。通过腹腔注射1次45 mg/kg链脲佐菌素(STZ)诱导糖尿病。在治疗组中,D+AG组在饮水中给予AG(1 g/L),D+M组大鼠腹腔注射M(10 mg/kg/d)。其中一组为未治疗的糖尿病组(D组)。所有动物在8周结束时安乐死。眼球摘除后,将眼睛固定在10%磷酸盐缓冲福尔马林中,石蜡包埋。进行组织化学染色,并在光学显微镜下检查标本。
8周后,糖尿病组大鼠的体重明显低于对照组、D+AG组和D+M组,血糖水平明显高于这些组。糖尿病导致基质显著水肿,上皮下基底膜中断。这些改变在D+AG组和D+M组中不明显或不存在。角膜、角膜上皮和基质的平均厚度在C组与D组、D组与D+AG组和D+M组之间存在统计学显著差异(P<0.05)。
长期给予AG和M可减轻链脲佐菌素诱导的糖尿病大鼠模型的角膜损伤。AG和M可能是治疗糖尿病角膜病变的潜在候选药物。然而,需要进一步研究以阐明这两种分子对糖尿病角膜并发症保护作用的机制。