The effects of supplemental melatonin administration on the healing of bone defects in streptozotocin-induced diabetic rats

ABSTRACT Diabetes mellitus (DM) causes an increased production of free radicals that can impair bone healing. Melatonin is a hormone secreted mainly by the pineal gland, which participates in the neutralization process of free radicals. Objective The aim of this study was to investigate histologic and biochemical effects of supplemental melatonin administration on bone healing and antioxidant defense mechanism in diabetic rats. Material and Methods Eighty-six Sprague-Dawley male rats were used in this study. Diabetes mellitus was induced by intraperitoneal (i.p.) administration of 65 mg/kg streptozotocin (STZ). Surgical bone defects were prepared in the tibia of each animal. Diabetic animals and those in control groups were treated either with daily melatonin (250 μg/animal/day/i.p.) diluted in ethanol, only ethanol, or sterile saline solution. Rats were humanely killed at the 10th and 30th postoperative days. Plasma levels of Advanced Oxidation Protein Products (AOPP), Malondialdehyde (MDA), and Superoxide Dismutase (SOD) were measured. The number of osteoblasts, blood vessels and the area of new mineralized tissue formation were calculated in histologic sections. Results At the 10th day, DM+MEL (rats receiving both STZ and melatonin) group had significantly higher number of osteoblasts and blood vessels as well as larger new mineralized tissue surfaces (p<0.05 for each) when compared with DM group. At the 30th day, DM group treated with melatonin had significantly lower levels of AOPP and MDA than those of DM group (p<0.05). Conclusion Melatonin administration in STZ induced diabetic rats reduced oxidative stress related biomarkers and showed beneficial effects on bone healing at short term.

【摘要】 糖尿病（Diabetes Mellitus, DM）可诱导机体产生过量自由基，进而损害骨愈合进程。褪黑素（Melatonin）主要由松果体（pineal gland）分泌，可参与自由基的中和过程。【目的】 本研究旨在探究外源性补充褪黑素对糖尿病大鼠骨愈合及抗氧化防御机制的组织学与生化影响。【材料与方法】 本研究共纳入86只雄性斯普拉格-道利（Sprague-Dawley）大鼠。通过腹腔内（intraperitoneal, i.p.）注射65 mg/kg链脲佐菌素（Streptozotocin, STZ）构建糖尿病模型。于每只大鼠胫骨部位制备手术骨缺损模型。将糖尿病造模大鼠与对照组大鼠分别予以每日腹腔注射稀释于乙醇的褪黑素（250 μg/只/日）、单纯乙醇注射或无菌生理盐水注射处理。分别于术后第10天和第30天对大鼠实施人道处死。检测血浆中晚期氧化蛋白产物（Advanced Oxidation Protein Products, AOPP）、丙二醛（Malondialdehyde, MDA）及超氧化物歧化酶（Superoxide Dismutase, SOD）水平，并对组织学切片中的成骨细胞数量、血管数量及新矿化组织形成面积进行定量统计。【结果】 术后第10天，与糖尿病模型组（DM组）相比，糖尿病+褪黑素干预组（DM+MEL，即同时接受链脲佐菌素与褪黑素处理的大鼠）的成骨细胞数量、血管数量及新矿化组织表面积均显著更高（各组比较p<0.05）。术后第30天，褪黑素处理的糖尿病模型组大鼠血浆AOPP及MDA水平均显著低于未处理的糖尿病模型组（p<0.05）。【结论】 对链脲佐菌素诱导的糖尿病大鼠补充褪黑素，可降低氧化应激相关生物标志物水平，并在短期干预中对骨愈合产生有益作用。