间歇性注射重组甲状旁腺激素对去卵巢大鼠骨组织形态计量学的影响

目的:观察甲状旁腺激素(PTH)间歇注射对月龄较老的去卵巢大鼠骨组织形态计量学的影响.方法:6月龄雌性SD大鼠被随机分成5组:(1)假手术基础组(ShamB),(2)去卵巢基础组(OVXB),(3)假手术终点组(ShamE),(4)去卵巢终点组(OVXE),(5)去卵巢后PTH治疗组(OVXE).ShamB和OVXB组大鼠于术后3个月、ShamE及OVXE和OVXEP组大鼠在术后4.5个月时处死并取骨.在术后3—4.5个月时给OVXE组大鼠每日皮下注射1次(6次/周)rhPTH_(1-84),给ShamE和OVXE组大鼠则注射rhPTH_(1-84)溶剂.对大鼠近端胫骨进行不脱钙切片以观察其骨组织形态计量学指标的变化.结果:OVXE组骨小梁面积百分比(TbAr)明显高于OVXE组(P<0.05),与OVXB组相似(P>0.05),但仍低于ShamE组(P<0.05);OVXE组的骨小梁厚度(TbTh)高于任何其他各组(P<0.05),其骨小梁数量(TbN)仅比OVXE组略高,其标记周长百分比(LPm)、矿化沉积率(MAR)和骨形成率(BFR/BV)均分别高于OVXE和ShamE组(P<0.01),而其破骨细胞数量(N of Oc)与后二组相似(P>0.05).结论:去卵巢后3个月的9月龄大鼠短期间歇注射rhPTH_(1-84)能阻止其骨量进一步减少,其作用机制是间歇注射PTH能增加TbTh而不明显改变TbN,能促进成骨活性而不影响破骨活性.

Effect of intermittent injection of recombinant human parathyroid hormone on bone histomorphometry of ovariectomized rats

AIM: To observe the effect of intermittent parathyroid hormone (PTH) administration on bone histomorphology of relatively old ovariectomized rats. METHODS: The 6-month-old female SD rats were randomly divided into 5 groups: (l) sham-operated for baseline (ShamB, n = 5), (2) ovariectomized for baseline (OVXB, n = 6), (3) Sham-operated for end point (ShamE, n - 6), (4) ovariectomized for end point (OVXE, n ?6), (5) ovariectomized for PTH treatment (OVXEP, n = 6). ShamB and OVXB rats were sacrificed 3 months after operation, ShamE, OVXE and OVXEP rats were sacrificed 4.5 months after operation. During 3 - 4.5 months after operation, OVXEP rats received daily subcutaneous injection of rhPTH1-84, while ShamE and OVXE received vehicle injection. The proximal tibiae of all rats were processed without decalcification for quantitive bone histomorphometry. RESULTS: The percent trabecular area ( TbAr) of OVXEP was significantly greater than that of OVXE (P<0.05), and was similar to that of OVXB (P>0.05), but was smaller than that of ShamE (P<0.05); the trabecular thickness (TbTh) of OVXEP was thicker than any other group (all, P<0.05); the trabecular number (TbN) of OVXEP was only slightly higher than that of OVXE; the percent labeled perimeter (LPm), mineral apposition rate(MAR) and bone formation rate with bone area as referent (BFR/BV) of OVXEP were all higher than those of ShamE and OVXE respectively ( P < 0.01), whereas the osteoclast number (N of Oc) of OVXEP was similar to those of ShamE and OVXE (P>0.05). CONCLUSION: Short-term intermittent injection of rhPTH1-84 can prevent further bone loss in 9-month-old rats 3 months after ovariectomy, the mechanisms of this therapy are that PTH could increase TbTh while not alter TbN, and promote bone-forming activity while not influence bone-resorptive activity.