去卵巢和抗骨质疏松干预后大鼠尿脱氧吡啶啉的变化

Changes of Urinary Deoxypyridinoline Crosslink/creatinine in Rats after Ovariectomy and Anti-osteoporotic Inter vention

目的观察大鼠去卵巢及予以不同的干预后尿脱氧吡啶啉/肌酐比率(urinarydeoxypyridinolinecrosslink/creatinine,UDpd/Cr)的变化,了解其在骨质疏松的诊断和治疗中的应用价值。方法将40只Wister大鼠于6月龄时行去卵巢手术(OVX,n=32)和假手术(Sham,n=8)。手术后6周分别予以不同的干预如下:OVX组(Ovx,n=8)和Sham组不做干预;雌激素干预组(O+E,n=9)予以17β雌二醇20μg/(kg·d),皮下注射;英卡膦酸钠干预组(O+C,n=7)予以Cimadronate0.2mg/(kg·d),经胃肠给药。手术后14周将大鼠处死,处死前收集24h尿液和血液测定血清及尿液中生化指标;处死后留取右侧股骨标本,进行股骨外周定量CT骨密度及股骨远端凹入实验生物力学测定。结果OVX组大鼠的骨吸收指标UDpd/Cr比Sham组增加了133.3%(P<0.01),OVX组大鼠尿钙/肌酐比率亦有增加,但与Sham组相比差异无显著性(P>0.05)。雌激素和英卡膦酸钠干预组UDpd/Cr比OVX组显著降低,分别减少了54.6%和51.8%(P均<0.01),并与Sham组接近。UDpd/Cr与骨量、骨密度及骨生物力学等指标的相关分析表明,其与以上指标之间存在显著负相关。结论UDpd/Cr是敏感的骨吸收指标,在OVX和予以雌激素、二膦酸盐干预后均有显著变化,其改变与骨密度及骨骼力学特性的改变密切相关。

Objective To observe the changes of urinary deoxypyridinoline crosslink/creatinine(UDpd/Cr)in rats after OVX and intervention by estrogen and bisphosphonate and investigate the possible application of deoxypyridinoline in osteoporosis diagnosis and treatment.Methods 40female6-month-old virginal Wistar rats were divided into5groups,ovariectomized or sham ovariectomized.(1)Ovxb (n=8):sacrificed at6weeks after OVX;(2)Sham (n=8):sham ovariectomized;(3)Ovxe (n=8):sacrificed at14weeks after OVX;(4)O+E (n=9):OVX+17βestradiol[20μg/(kg·d)ih];(5)O+C(n=7):OVX+cimadronate [0.2mg /(kg·d)];Treatment started6weeks after OVX and lasted8weeks.Rats in group2～5were sacrificed at14weeks after OVX.Urinary and serum biochemical parameters were measured,pQCT scanning of femur,bone biomechanical test in femur were determined.Results OVX resulted in increasing of UDpd/Cr 133.3%(P<0.01).The ratio of UCa /Cr also increased in OVX groups but without any significant compared with Sham (P>0.05).UDpd/Cr were reduced by54.6%and51.8%(P<0.01)in O+E,O+C group respectively compared with Ovxe.The significant negative correlationships were found between UDpd/Cr and bone mass,BMD and biomechanic characteristics.Conclusions UDpd/Cr ratio is a sensitive bone resorption marker,a marked changes were observed when the rats ovariectomized or treated with estradiol and cimadronate.There were best correlation between UDpd/Cr and bone minral density and bone biomechanic characteristics.It is fair to apply UDpd/Cr ratio for osteoporosis diagnosis and treatment.