Drug distribution of melatonin in bone tissue and improvement of bone microstructure in type 2 diabetic osteoporosis rats / 中华骨科杂志

ABSTRACT

Objective:To investigate the medicinal retention of different concentrations of melatonin in the bone tissue of type 2 diabetic osteoporosis (T2DOP) rats and explore to efficacy of improvement of the bone microstructure of T2DOP rats.Methods:A total of 95 SD rats were selected, 60 of which had intraperitoneal in jection of high-fat diet combined with low-dose streptozotocin establishing a T2DOP rat model. Two months later, 45 rats' model was determined to be successful by detecting blood glucose and insulin sensitivity index. 30 successful modelling and 30 normal SD rats were randomly selected for melatonin distribution experiment, and were divided into four groups according to the injected melatonin concentration, including modeling rat high concentration group (50 mg/kg), modeling rat low concentration group (10 mg/kg), normal rat high concentration group (50 mg/kg) and normal rat low concentration (10 mg/kg), and there were15 rats in each group. Each group was divided into 5 sub-groups according to the time point of sampling (5, 15, 30, 60, 120 min), 3 animals per group. The bone tissue of each group was pretreated, and then the melatonin drug distribution in the bone tissue was detected by high performance liquid chromatography (HPLC). Another 15 rats were successfully modeled, and were divided into T2DOP group, high melatonin group (50 mg/kg) and low melatonin group (10 mg/kg), 5 rats in each group. 5 normal SD rats were taken as controls (control group), and Micro-CT was used to detect changes in bone microstructure after 8 weeks of treatment with melatonin.Results:The results of the drug distribution experiment showed that after melatonin was injected intraperitoneally, there were drugs remaining in the bone tissues of the rats in each group. The drug concentration reached the highest after 30 min of administration, and significantly decreased after 120 min. Compared with the normal rat low concentration group, there was no significant difference in the drug concentration between the two groups at 5 time points. However, the drug concentration at the four time points of 5, 15, 30, and 60 min in the modeling rat high concentration group were 7.613±2.568 ng/ml, 13.983±2.262 ng/ml, 18.816±1.291 ng/ml, 6.172±1.962 ng/ml, 1.112±0.566 ng/ml, which were significantly different compared with normal rat high group. Micro-CT results showed that after 8 weeks of melatonin treatment, the bone density of the high concentration group was (205.72±28.41 g/cm 3) significantly lower than that in the low concentration group (223.63±35.41 g/cm 3), but both groups were significantly higher than the normal rat group (158.31±31.86 g/cm 3). Conclusion:Exogenous melatonin is distributed in bone tissue, and the drug absorption rate of T2DOP rats is higher. Meanwhile, there is no difference in the distribution of melatonin in bone tissue with different concentrations, and these two concentrations of melatonincan canimprove the bone microstructure of T2DOP rats.