比较褪黑素与维生素E在对抗早期糖尿病大鼠膀胱氧化性损伤的作用

Role of melatonin and vitamin E in resisting oxidative damage of diabetic rat bladder at early stage

目的:研究褪黑素与维生素E在保护糖尿病大鼠膀胱氧化应激损伤,预防糖尿病中由于氧化剂和抗氧化剂平衡失调导致的并发症中的作用。方法:将链脲佐菌素(streptozocin,STZ)诱导的糖尿病大鼠随机分为3组,分别为糖尿病非治疗组,维生素E治疗组和褪黑素治疗组,对维生素E治疗组和褪黑素治疗组分别给予维生素E(50 mg/kg)和褪黑素(2 mg/kg)腹腔注射治疗,未作处理的大鼠作为正常对照组,糖尿病非治疗组和正常对照组腹腔注射等体积含4%乙醇的生理盐水,每组每天给药1次,共注射4周,实验结束后,观察各组膀胱组织超微结构的变化。取所有实验大鼠膀胱组织观察膀胱组织中丙二醛(malondi-aldehyde,MDA)、还原型谷胱甘肽(glutathione,GSH)、超氧化物歧化酶(superoxide dismutase,SOD)活性的变化。结果:电镜结果显示,糖尿病非治疗组大鼠膀胱组织平滑肌细胞线粒体明显肿胀、空化,可见血管内皮细胞和成纤维细胞线粒体肿胀、空化,胞质内可见坏死线粒体,而维生素E治疗组和褪黑素治疗组所见均较糖尿病非治疗组轻。与正常对照大鼠比较,糖尿病非治疗大鼠膀胱组织MDA含量明显升高,GSH含量降低,SOD活性显著降低(均P<0.01)。与糖尿病非治疗组相比,给予褪黑素、维生素E治疗后可明显降低膀胱组织中MDA含量,使GSH含量上升,并增强SOD活性(均P<0.01)。2种抗氧化剂在膀胱组织中作用相比,褪黑素在降低MDA含量与增加GSH含量强于维生素E(均P<0.01),但在增强SOD活性方面褪黑素与维生素E无明显差异(P=0.512)。结论:研究结果表明,褪黑素和维生素E能有效地调节糖尿病大鼠膀胱组织的氧化应激反应,保护平滑肌细胞,血管内皮细胞和成纤维细胞线粒体,其中褪黑素的保护作用明显强于维生素E。

Objective：To study the role of melatonin and vitamin E in protecting bladder tissues of diabetic rats from oxidative stress injury and complications caused by the imbalance between oxidants and antioxidants. Methods：Diabetic rat models were established through lumbar injection of streptozotocin and the rats were divided into three groups：diabetic control group,vitamin E treatment group and melatonin treatment group. Besides, another normal control group was brought in the experiment. Vitamin E （50 mg/kg） and melatonin（2 mg/kg） were respectively given to rats in vitamin E treatment group and melatonin treatment group. Rats in diabetic control group and normal control group received 4% ethanol physiological saline with a dosage of 2 ml/kg once daily. After four weeks＇ injection,changes in uhrastructures of the samples were observed by electron microscope and changes in malonaldehyde （MDA）, glu- tathione（GSH） and superoxide dismutase（SOD） of the bladder samples were measured. Results：Results of electron microscope of diabetic control group showed that mitochondrias of smooth muscle cells,vessel endothelial cells and mechanocytes were swelling and cavitating and thrombus-like structure was observed,which was much milder in vitamin E treatment group and melatonin treatment group than in diabetic group. Compared with those in normal control group, MDA of diabetic control group was distinctly elevated （P〈 0.01 ）, while GSH （P〈0.01 ） and SOD （P〈0.01） were markedly lowered. After treatment with vitamin E and melatonin, MDA was obviously declined（P〈0.01 ） ,GSH（P〈0.01 ） and SOD（P〈0.01 ） were strengthened. Effects of melatonin on decreasing MDA and increasing GSH were much stronger than those of vitamin E（P〈0.01 ）, while there was no significant difference in enhancing SOD activity between melatonin and vitamin E （P=0.512）. Conclusions： Melatonin and vitamin E could regulate oxidative stress in the bladder tissues of diabetic rats and protect the mitochondrias of smooth musle cells, vessel endothelial ceils and mechanocytes. The protective effect of melatonin is stronger than that of vitamin E.