比较雷奈酸锶与甲状旁腺激素(1-34)对卵巢切除大鼠骨质量的影响

Comparison of the Effects of Strontium Ranelate and PTH(1-34) on Bone Quality of Ovariectomized Rats

目的：比较雷奈酸锶与甲状旁腺激素（1-34）对卵巢切除大鼠骨质量的影响。方法：80只SD大鼠,分别接受假手术（A组,n=10）和双侧卵巢切除（B组,n=70）手术,术后3个月B组大鼠随机分为7组,每组10只。分别sc生理盐水[0.9 g/（kg·d）,B0组];ig雷奈酸锶低、中、高剂量[0.45、0.9、1.35g/（kg·d）,B1～B3组];sc甲状旁腺激素（1-34）低、中、高剂量[30、60、90μg/（kg·d）,连续给药5 d后停止给药2 d,B4～B6组],A组大鼠给药方案同B0组。8周后处死所有大鼠,酶联免疫吸附法（ELISA）检测大鼠血清1型前胶原氨基末端肽（P1NP）、1型胶原C端肽（CTX-1）含量;骨密度仪检测第4腰椎骨密度;微电子计算机断层扫描（CT）检测松质骨相对体积（BV/TV）、骨小梁厚度（Tb.Th）、骨小梁数量（Tb.N）和骨小梁分离度（Tb.Sp）;压缩试验检测第5腰椎最大载荷和弹性模量。结果：与A组比较,B0～B6组大鼠血清P1NP、CTX-1水平显著升高,第4腰椎骨密度、第5腰椎最大载荷、弹性模量显著降低（P〈0.05）;B0组大鼠第4腰椎BV/TV水平显著降低、Tb.Sp水平显著升高（P〈0.05）。与B0组比较,B1～B3组大鼠第4腰椎骨密度、第5腰椎最大载荷、弹性模量显著升高（P〈0.05）;B4～B6组大鼠P1NP含量、BV/TV、Tb.N水平、第4腰椎骨密度、第5腰椎最大载荷、弹性模量显著升高,且高于B1～B3组（P〈0.05）;B1～B6组大鼠Tb.Sp水平显著降低,且B4～B6组低于B1～B3组（P〈0.05）。8组大鼠Tb.Th水平比较,B0～B6组大鼠CTX-1含量比较,差异均无统计学意义（P〉0.05）。结论：甲状旁腺激素（1-34）抑制去卵巢大鼠骨丢失、改善其椎体骨微观结构和生物力学性能的作用强于雷奈酸锶。

OBJECTIVE：To compare the effects of strontium ranelate and PTH（1-34）on bone quality of ovariectomized rats.METHODS：80 SD rats were randomly divided into sham operation group（group A,n=10）and dual ovariectomy（group B,n=70）.3 months after operation,group B were randomly divided into 7 groups,with 10 rats in each group.B0 group were given normal saline [0.9 g/（kg·d）] subcutaneously;B1-B3 groups were given low-dose,medium-dose and high-dose of strontium ranelate[0.45,0.9,1.35 g/（kg·d）] intragastrically;B4-B6 groups were given low-dose,medium-dose and high-dose of PTH（1-34）[30,60,90 μg/（kg·d）,treated for 5 days,rested for 2 days] subcutaneously.Group A was same to group B0 in therapy regimen.All rats were sacrificed 8 weeks later.The contents of P1 NP and CTX-1 in serum of rats were determined by ELISA assay;bone density of 4th lumbar vertebrae was detected by bone densitometer;BV/TV,Tb.Th,Tb.N and Tb.Sp were detected by CT;maximal load and elastic modulus of 5th lumbar vertebrae were measured by compression test.RESULTS：Compared with group A,the serum levels of P1 NP and CTX-1 in B0-B6 groups increased significantly,while bone density of 4th lumbar vertebrae,maximal load and elastic modulus of 5th lumbar vertebrae decreased significantly in B0-B3 groups（P〈0.05）;BV/TV level of 4th lumbar vertebrae decreased significantly,while Tb.Sp level increased significantly in B0 group（P〈0.05）.Compared with B0 group,bone density of 4th lumbar vertebrae,maximal load and elastic modulus of 5th lumbar vertebrae increased significantly in B1-B3 groups（P〈0.05）;P1NP content,BV/TV,Tb.N level,bone density of 4th lumbar vertebrae,maximal load and elastic modulus of 5th lumbar vertebrae increased significantly in B4-B6 groups,and were higher than in B1-B3 groups（P〈0.05）.Tb.Sp level of B1-B6 groups decreased significantly and were lower than those of B1-B3 groups（P〈0.05）.There was no statistical significance in Tb.Th level among 8 groups and CTX-1 content among B0-B6 groups（P〈0.05）.CONCLUSIONS：PTH（1-34）is better than strontium ranelate in inhibiting bone loss,improving vertebral bone micro-structure and biomechanical properties of ovariectomized rats.