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  

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

作　　者：简小冲[1] 陈江[1] 黄文秀[1] 杜志斌[1] 

机构地区：[1]福建医科大学附属口腔医院种植中心,福建福州350002

出　　处：《南京医科大学学报（自然科学版）》2007年第11期1217-1220,I0001,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：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)

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。Objective：To investigate the effect of simvastain on the expression of BMP-2 and Smadl/5 in rats with ovariectomy-induced osteoporosis ,and thus elucidate the mechanism of BMP-2 and Smadl/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 Smadl/5 positive cells and Smadl/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.

关 键 词：骨质疏松 辛伐他汀 骨形成蛋白-2 信号转导 Smad1/5 

分 类 号：R782.12[医药卫生—口腔医学]