甲状旁腺激素1-34和雷奈酸锶联合使用对去势大鼠骨质疏松症影响的研究

Effect of combined use of parathyroid hormone 1-34 and strontium ranelate on osteoporosis in ovariectomized rats

关键词:  去势大鼠  骨质疏松症  甲状旁腺激素1-34  雷奈酸锶

Key words:  ovariectomized rats  osteoporosis  parathyroid hormone 1-34  strontium ranelate

摘要:

目的　研究联合使用甲状旁腺激素1-34 (PTH)和雷奈酸锶(SR)对去势大鼠骨质疏松症的影响。方法　50只雌性SD大鼠进行假手术(Sham组,n=5)及双侧去卵巢手术(OVX组,n=45),正常情况下饲养12周，取全部Sham组并随机取5只OVX组大鼠检查骨质疏松模型的建立情况。随后所有的OVX组大鼠随机平均分成4组（10只/组）：OVX对照组、SR组、PTH组和PTH+SR组；SR组、PTH组和PTH+SR组分别给予SR灌胃（625 mg/kg，每周5次）、PTH皮下注射（20 μg/kg，每天1次）和相同剂量的SR灌胃及PTH皮下注射。药物治疗8周后将所有大鼠处死取胫骨行骨密度及微观参数检测，最大载荷及弹性模量的测定和血清P1NP、CTX-1含量的测定。结果　骨质疏松大鼠模型建立成功。与和OVX对照组相比，SR组、PTH组和PTH+SR组各组大鼠胫骨骨密度显著增加，骨小梁数量增加。与OVX对照组比较，SR、PTH及PTH+SR组的Tb.N、Tb.Th、BV/TV及conn.D明显增加，Tb.Sp明显降低，差异有显著性意义，P<0.05。SR组、PTH组和PTH+SR组的胫骨最大载荷及刚度值均高于OVX对照组；与OVX对照组比较，SR、PTH及PTH+SR组大鼠血清中P/NP与CTX-1表达升高，差异有显著性意义，P<0.05。结论　联合使用PTH和SR可以明显增强去势大鼠成骨活性，增加其骨密度，增强骨强度，对去势大鼠骨质疏松症的治疗有叠加作用。

Abstract:

Objective 　 To investigate the effect of combined use of parathyroid hormone 1-34 (PTH) and strontium ranelate (SR) on osteoporosis in ovariectomized rats.　Methods 　 Fifty female SD rats were sham operated (Sham,n=5) and ovariectomized (OVX,n=45). After 12 weeks, five rats of each group were randomly selected to test the establishment of osteoporosis model. Then all rats in OVX group were randomly divided into 4 groups（10 rats /group）: OVX group, SR group, PTH group and PTH+SR group. The rats were given 625 mg/kg SR, 5 times a week by intragastric administration in SR group, 20 μg/kg PTH once a day by subcutaneous injection in PTH group, and the combined use of SR and PTH in PTH+SR group. After 8 weeks of drug treatment, all rats were executed to examine the tibia by Micro-CT examination, maximum load and elastic modulus, and test serum P1NP and CTX-1 levels. 　Results 　 Compared with the OVX group, bone mineral density increased, bone histomorphometry parameters improved, and bone metabolism enhanced in SR group, PTH group and SR+PTH group. There was the highest BMD, Tb.N, Tb.Th, BV/TV, Conn.D and the strongest osteogenic activity and lowest Tb. Sp in SR+PTH group than other two treatment groups (P<0.05). The Bone quality were also significantly improved in SR group and PTH group, but less than that in SR+PTH group. 　Conclusion 　 PTH and SR can significantly enhance the osteogenic activity, increase the bone mineral density, and enhance the strength of the bone, and they have a superposition effect on osteoporosis in ovariectomized rats.