雷洛昔芬上调卵巢切除大鼠腰椎护骨素mRNA的表达

Raloxifene up-regulates the mRNA expression of osteoprotegerin in the lumbar vertebra of ovariectomized rats

目的建立绝经后骨质疏松(postmenopausalosteoporosis,PMOP)的大鼠模型,研究雷洛昔芬(raloxifene,RLX)对卵巢切除大鼠腰椎组织中护骨素(OPG)基因mRNA表达水平的影响,探讨其治疗PMOP的作用机制。方法6月龄未交配健康雌性SD大鼠40只,随机分为假手术(SHAM)组,卵巢切除(OVX)组,OVX+戊酸雌二醇(E2)组和OVX+RLX组。灌胃13周后处死动物,第四腰椎行骨组织形态计量指标测定,第二腰椎采用RT-PCR方法,对OPGmRNA表达水平进行检测。结果OVX组大鼠较SHAM组骨小梁体积百分比(TBV%)显著下降;类骨质体积百分比(OSV%)明显升高(P<0.05);E2和RLX组大鼠的TBV%明显升高,OSV%明显下降;OPGmRNA表达水平在OVX大鼠组织中下调,与SHAM组相比有显著性差异(P<0.05),E2和RLX均可上调OVX大鼠骨组织OPGmRNA表达水平(P<0.05)。结论实验成功制造了大鼠PMOP模型;E2和RLX均可抑制骨转换;PMOP的发生与OPG有关,RLX和E2一样,其抗骨吸收效应很可能是通过OPG介导的。

Objective To establish a postmenopausal osteoporotic model of rats and investigate the effect of raloxifene（RLX） on the expression of OPG mRNA in lumbar vertebra of ovariectomizod rats, and to analyze its mechanism in the prevention of postmenopausal osteoporosis. Methods Forty female rats of 6-month-old were randomly allocated into 4 groups： sham operated group, ovariectomized group （OVX）, ovariectomlzed ＋ valerate estradiol group（OVX ＋ E2 ）, and ovariectomized ＋ raloxifene group（OVX ＋ RLX）. All rats were sacrificed after lavaged for 13 weeks. The fourth lumbar vertebra was dissected for histomorphology and the second lumbar vertebra for measurement of OPG mRNA by reverse transcription polymerase chain reaction technique. Results The trabecular volume% was significantly lower in the OVX group than that in the SHAM group, while the ostoid seam% was significantly higher （P 〈 0.05）. The trabecular volume% Was increased and ostoid seam% was reduced in OVX ＋E2 group and OVX ＋ RLX group. Compared with the SHAM rats, the OPG mRNA level was decreased significantly in the OVX group （ P 〈 0.05）, and E2 and RXL up-regulated the expression of OPG mRNA significantly （ P 〈 0.05）. Conclusions The rat model of postmenopausal osteoporosis is successfully established. Valerate estradiol and RXL can inhibit bone turnover. OVX-induced bone loss is associated with OPG. Raloxifene, as well as valerate estradiol, might have anti-resorbtion effect on bone mediated by OPG.