辛伐他汀对去卵巢骨质疏松大鼠骨组织BMP-2及信号转导蛋白Smad1/5表达的影响
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福建省科技攻关计划重点资助(2003Y025);福建医科大学教授学术发展基金(JS06104)


The effect of simvastatin on BMP-2 and the signal transduction protein(Smad1/5) expression in the bone of ovariectomized rats
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    摘要:

    目的:研究辛伐他汀对去卵巢(OVX)骨质疏松大鼠骨形成蛋白BMP-2及其信号转导蛋白Smad1/5表达的调节,探讨BMP-2及其信号转导蛋白Smad1/5在骨质疏松发病机制中的作用机制及辛伐他汀对其调节作用。方法:54只3个月龄雌性SD大鼠,随机分成3组,实验组、对照组、模型组,每组18只。适应性喂养1周后进行手术,术后8周开始给药,实验组给予辛伐他汀5 mg/(kg·d)灌胃,其余2组用等量生理盐水灌胃。用药后第4周每组随机处死半数大鼠,12周后处死剩余大鼠,分离胫骨,免疫组化检测胫骨干骺端BMP-2及其信号转导蛋白Smad1/5的表达。结果:①用药4周,大鼠胫骨干骺端BMP-2表达:实验组、对照组较模型组增加(P < 0.05或P < 0.01);②用药12周,大鼠胫骨干骺端BMP-2表达、Smad1/5表达:实验组、对照组较模型组增加(P < 0.05或P < 0.01);③用药12周较4周,实验组Smad1/5表达明显增加(P < 0.01)。结论:BMP-2及信号转导蛋白Smad1/5表达水平的下调可能是原发性骨质疏松发生的重要机制,辛伐他汀能上调BMP-2的表达,长期用药能促进信号转导蛋白Smads1/5的表达,可能与其防治绝经后骨质疏松症的作用机制有关。

    Abstract:

    Objective:To investigate the effect of simvastain on the expression of BMP-2 and Smad1/5 in rats with ovariectomy-induced osteoporosis,and thus elucidate the mechanism of BMP-2 and Smad1/5 in nosogeny of osteoporosis and the regulating effect of simvastain. Methods:54 female SD rats were divided into three groups randomly:the experimental group,control group and model group .8 weeks after ovariectomy and sham-operation, simvastatin of 5 mg/(kg·d) were administered orally to the experimental group, and normal saline to the other two groups. Half of the rats were killed separately 4 weeks and 12 weeks after administration. Expression of BMP-2 and Smadl/5 in metaphysis of tibia was detected by immunochistochemistry. Results:① 4 weeks after administration,expression of BMP-2 was higher in experimental group and control group than that in model group(P < 0.05 or P < 0.01); ②12 weeks after administration,expression of BMP-2 and Smadl/5 was higher in experimental group and control group than that in model group(P < 0.05 or P < 0.01); ③Number of Smad1/5 positive cells and Smad1/5 gradation in experimental group was higher at 12 weeks after administration than 4 weeks(P < 0.01). Conclusion:Hypo-expression of BMP-2 and Smadl/5 may be an important mechanism in nosogeny of primary osteoporosis. Simvastain can up-regulate BMP-2 expression in bone. Long-time administration of Simvastain can up-regulate Smadl/5 expression that may be an important mechanism of prevention and cure of osteoporosis.

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简小冲,陈 江,黄文秀,杜志斌.辛伐他汀对去卵巢骨质疏松大鼠骨组织BMP-2及信号转导蛋白Smad1/5表达的影响[J].南京医科大学学报(自然科学版),2007,(11):1217-1220

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  • 收稿日期:2007-05-09
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