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

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(20μg/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 ovarieetomized rats. Methods Fifty female SD rats were sham operated （Sham, n = 5 ） and ovarieetomized （OVX, tr = 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 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 com-bined 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 parameter 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.