去势法兔骨质疏松模型建立的探讨

Establishment of rabbit osteoporosis model by ovariectomy

目的探讨采用去势法建立免骨质疏松症模型的可行性。方法将20只5月龄新西兰雌兔随机分成手术组(OVX)与假手术组(SHAM),手术组行双侧卵巢切除。两组分别于术前、术后 4、8、12、24 w进行全身骨密度(BMD)检测;术前、术后12 w和术后24 w行骨代谢指标检测: 骨特异性碱性磷酸酶(BALP)、骨钙素(BGP)、抗酒石酸酸性磷酸酶-5b(TRAP-5b);于术后 12w和24w各处死10只兔,取其右侧股骨行生物力学测定及取腰椎,制成不脱钙的骨切片,行骨组织形态计量学分析。结果去势6 m后,OVX组全身BMD明显低于SHAM(P<0．01):在骨代谢指标TRAP-5b、BALP及BGP,OVX组均明显高于SHAM组(P<0．01):生物力学检测中的弯曲强度、比例载荷、最大挠度和弯曲破坏载荷OVX组均较SHAM组明显下降(P<0．01)。骨组织形态计量学显示,OVX组的骨质丢失明显增加(BV／TV％下降,Tb．N减少,Tb．Sp变宽),骨小梁形成明显减少(OS／BS及MAR均增多),骨吸收明显升高(ES／BS、Oc．No／Tb．Pm 升高),这些指标与SHAM组比较有明显性差异(P<0．01)。结论去势法建立兔骨质疏松症模型切实可行,5月龄雌兔,造模6月。本模型为探明原发性骨质疏松发病机理、评价药物疗效及临床骨质疏松性假体松动研究提供重要的基础。

Objective To investigate the establishment of rabbit osteoporotic model by ovariectomy. Methods Twenty New Zealand rabbits were divided into two groups equally: operation group (OVX) and shame operation group (SHAM). The bilateral ovaries of the OVX were ectomized, while those of the SHAM were not. The BMD was measured before and 4, 8, 12, 16 and 24 weeks after the operation. The BALP, BGP and TRAP-5b, indicators, bone metabolism indicators, were observed before and 12 and 24 weeks after operation. Ten rabbits were sacrificed at 12 and 24 weeks post-operation respectively and specimens of right femurs were sectioned for biomechanical test and the third lumbar vertebra for the histomorphometry. Results After six months of the operation, the BMD in the OVX group was lower than that of the SHAM' s (P<0. 01). While the levels BALP, BGP and TRAP-5b were higher (P<0. 01) .All the biomechanics markers, such as winding destroy, proportion load, maximum deflection and winging strength, in the OVX showed less strength than the SHAM' s (P<0. 01) . More increased bone loss, significantly reduced remodeling of trabecular and bone resorption was shown in the OVX group (P<0. 01) . Conclusions Ovariectomy is a good way to establish New Zealand rabbit model of osteoporosis. The rabbits should be five months old and the whole procedures takes six months. This study makes it possible for further study of osteoporosis.