褪黑素对糖尿病大鼠视网膜组织中氧化应激反应及ICAM-1表达的影响

目的观察褪黑素对糖尿病（DM）大鼠氧化应激和视网膜组织中细胞间黏附分子-1（ICAM-1）表达的影响。方法36只Wistar大鼠随机取10只作为正常对照组;其余26只制成DM模型,将造模成功的20只大鼠随机分为褪黑素组和DM组,每组10只。褪黑素组大鼠每日左下腹腔注射10 mg/kg褪黑素进行干预治疗,正常对照组和DM组大鼠不进行治疗。12周后测各组大鼠的体重、血糖、血清一氧化氮（NO）及血清超氧化物歧化酶（SOD）值,并观察大鼠视网膜形态以及ICAM-1表达的不同。结果12周后,与正常对照组比较,DM组和褪黑素组大鼠体重均明显下降（t=5.15,t=3.62;P〈0.05）,血糖均升高（t=69.03,t=45.78;P〈0.05）,而DM组和褪黑素组体重（t=1.88,P=0.09）和血糖（t=-1.41,P=0.19）比较,差异均无统计学意义。与正常对照组比较,DM组和褪黑素组大鼠血清中SOD、NO水平均明显下降（P〈0.05）;与DM组比较,褪黑素组大鼠血清SOD值、血清NO水平均明显升高（t=9.45,t=2.11,P〈0.05）。组织病理学检查显示,DM组和褪黑素组大鼠视网膜结构紊乱,白细胞黏附于血管内皮;免疫组织化学检测显示2组大鼠视网膜标本中ICAM-1颗粒表达于视网膜血管内皮细胞,但褪黑素组较DM组表达明显降低。结论褪黑素可显著提高DM大鼠体内抗氧化能力、降低炎症反应,对DM引起的视网膜损伤有一定的保护作用。

Effects of melatonin on oxidative stress and the expression of ICAM-1 on retina in diabetic rat

Background Research demonstrates that oxidative stress is associated with inflammatory response.Melatonin is verified to be an antioxidant.But,the effects of melatonin on the retinal inflammation in the eye with diabetic retinopathy（DR） is below understood.ObjectiveThe aim of the present study is to investigate the effect of melatonin on oxidative stress and the expression of ICAM-1 on retina in diabetic rat.MethodsDiabetes mellitus（DM） animal models were established in 26 Wistar rats by intraperitoneal injection of streptozocin（STZ）,and 20 successful models were used in this study.Melatonin with the dose 10mg/（kg.d） was administered by intraperitoneal injection for 12 weeks.Ten normal Wistar rats were as control group.The body weight,blood glucose,serum superoxide dismutase（SOD）,serum nitric oxide（NO） of experimental rats were detected.The eyeballs of rats were obtained and the retinas were prepared for the histologic examination.The expression of intercellular cell adhesion molecule-1（ICAM-1） in rat retina was detected by immunochemistry.ResultsThe body weight was significantly declined in DM group and melatonin group in comparison with normal control group（t=5.15,t=3.62,P0.05）,but that of melatonin was insignificantly increased in melatonin group compared with DM group（t=1.88,P=0.09）.The blood glucose level was evidently higher in DM group and melatonin group than normal control group（t=69.03,t=45.78,P0.05）;while no significant difference was seen between melatonin group and DM group（t=-1.41,P=0.19）.Compared with normal control group,the levels of serum SOD and serum NO were significantly decreased in DM group and melatonin group（P0.05）,and those of melatonin group were obviously higher than DM group（t=9.45,t=2.11,P=0.05）.The histologic examination showed that the retinal structure was obvious disorder and lots of leucocytes were found around the capillary vessels,however,the retinal structure was significantly improved in melatonin group.The immunochemistry revealed that ICAM-1 was strongly expressed in lots of endothelial cells of retinal capillary vessels in DM group,but the numbers of the positive cells was decreased in melatonin group.ConclusionMelatonin exerts a protective role to the retina of diabetic rats through enhancing the antioxidant capability and decreasing the inflammatory reaction.