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

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大鼠随机分为假手术组(Sham组,n=5)及双侧去卵巢手术组(OVX组,n=45),正常情况下饲养12周后,随机取5只OVX组大鼠和5只Sham组大鼠处死,取胫骨检查骨质疏松模型的建立情况.随后剩下的40只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,差异均有显著性意义,P＜0.05.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组的胫骨最大栽荷及刚度值均高于OVX对照组;与OVX对照组比较,SR、PTH及PTH+ SR组大鼠血清中P1NP表达量增加,而CTX-1表达降低,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.%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 randomdy divided into 4 groups(10 rats/group):OVX control 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 g/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 tibial bone mineral density and bone histomorphometry parameters,maximum load and elastic modulus,and test serum P1NP and CTX-1 levels.Results Osteoporosis rat model was established successfully.And compared with the OVX control group,bone mineral density increased and bone histomorphometry parameters improved in SR group,PTH group and SR + PTH group.Compared with the OVX control group,Tb.N,Tb.Th,BV/TV,Conn.D improved and Tb.Sp reduced evidently in SR group,PTH group and SR + PTH group,and the difference was statistically significant(P ＜0.05).The maximum load and stiffness of tibia in SR group,PTH group and SR + PTH group were higher than OVX group;compared with the OVX control group,the P1NP parameter of rats serum improved and the CTX-1 paraneter of rats serum reduced in SR group,PTH group and SR + PTH group,and the difference was statistically significant (P ＜ 0.05).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.