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松果体切除和褪黑素给药对大鼠实验性骨质疏松症中骨代谢生化标志物动态模式的影响。

The influence of pinealectomy and melatonin administration on the dynamic pattern of biochemical markers of bone metabolism in experimental osteoporosis in the rat.

作者信息

Ostrowska Zofia, Kos-Kudla Beata, Marek Bogdan, Kajdaniuk Dariusz, Staszewicz Pawel, Szapska Bozena, Strzelczyk Janusz

机构信息

Department of Clinical Biochemistry, Silesian Medical Academy, Zabrze, Poland.

出版信息

Neuro Endocrinol Lett. 2002 Apr;23 Suppl 1:104-9.

Abstract

BACKGROUND AND OBJECTIVES

There have been suggestions in literature that characteristic changes of bone mass in osteoporosis may be related to the melatonin (Mel): The aim of this study was to demonstrate whether pinealectomy and Mel administration can affect postmenopausal osteoporosis processes induced in female rats by way of ovariectomy.

METHODS

The study included 198 animals; 6 remained intact (0), 96 were ovariectomized (Ox), and the remaining ones underwent a sham operation (SOx). Two weeks after surgery, the rats were divided into eight groups: 1) SOx + SPx, 2) SOx + SPx + Mel, 3) Ox + SPx, 4) Ox + SPx + Mel, 5) SOx + Px, 6) SOx + Px + Mel, 7) Ox + Px, 8) Ox + Px + Mel. Animals from the 5th, 6th, 7th and 8th groups were pinealectomized (Px) while the remaining ones underwent a sham operation (SPx). Two weeks after surgery Mel (50microg/100g of bm) were administered intraperitoneally in rats in the 2nd, 4th, 6th and 8th groups while the remaining animals were administered with solvent only (5% solution of ethyl alcohol in physiological saline). Rats were administered the Mel solution or the solvent daily between 5 and 6 pm during a 4-week period. At the appropriate time, i.e. prior to surgery (group 0) and after 6, 12, 18 and 24 weeks from Px or SPx (time subgroups a, b, c and d) the animals were placed separately in metabolic cages (from 6.30 until 9.30 am) in order to collect urine aliquots for HYP and Ca determinations. The blood for the assay of ALP, PICP and ICTP was collected within the next 24 hours at 8 am (rats killed by decapitation).

RESULTS

The study has shown that pinealectomy had inducing, while exogenous Mel suppressing effect upon the level of investigated markers of bone metabolism; these changes were more pronounced in ovariectomized rats. Administration of Mel only partially levelled changes of bone metabolism caused by pinealectomy. In rats with preserved pineal gland effect of Mel on bone turnover markers was less pronounced. After discontinuing administration of Mel distinct tendency to increase studied biochemical markers of bone metabolism was shown.

CONCLUSION

Our findings suggest that Mel is an important modulator of experimental osteoporosis processes induced in female rats by way of ovariectomy.

摘要

背景与目的

文献中曾有观点认为,骨质疏松症中骨量的特征性变化可能与褪黑素(Mel)有关。本研究的目的是证实松果体切除及给予Mel是否会影响雌性大鼠因卵巢切除诱导的绝经后骨质疏松进程。

方法

本研究纳入198只动物;6只保持完整(0组),96只接受卵巢切除(Ox组),其余接受假手术(SOx组)。术后两周,将大鼠分为八组:1)SOx + SPx组,2)SOx + SPx + Mel组,3)Ox + SPx组,4)Ox + SPx + Mel组,5)SOx + Px组,6)SOx + Px + Mel组,7)Ox + Px组,8)Ox + Px + Mel组。第5、6、7和8组动物接受松果体切除(Px),其余接受假手术(SPx)。术后两周,第2、4、6和8组大鼠腹腔注射Mel(50μg/100g体重),其余动物仅给予溶剂(5%乙醇生理盐水溶液)。在4周内,大鼠于每天下午5至6点给予Mel溶液或溶剂。在适当时间,即手术前(0组)以及Px或SPx术后6、12、18和24周(时间亚组a、b、c和d),将动物分别置于代谢笼中(上午6:30至9:30),以收集尿液样本用于羟脯氨酸(HYP)和钙测定。在接下来的24小时内上午8点采集血液用于碱性磷酸酶(ALP)、I型前胶原羧基端前肽(PICP)和I型胶原羧基端肽(ICTP)检测(大鼠断头处死)。

结果

研究表明,松果体切除对所研究的骨代谢标志物水平有诱导作用,而外源性Mel有抑制作用;这些变化在卵巢切除大鼠中更明显。给予Mel仅部分缓解了松果体切除引起的骨代谢变化。在松果体完整的大鼠中,Mel对骨转换标志物的作用不太明显。停止给予Mel后,所研究的骨代谢生化标志物显示出明显的升高趋势。

结论

我们的研究结果表明,Mel是雌性大鼠因卵巢切除诱导的实验性骨质疏松进程的重要调节因子。

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