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甲状旁腺激素(1-34)增加了老年雌性大鼠的全身骨量。

Parathyroid hormone (1-34) increased total body bone mass in aged female rats.

作者信息

Simmons H A, Pirie C M, Thompson D D, Ke H Z

机构信息

Department of Cardiovascular and Metabolic Diseases, Pfizer Central Research, Groton, Connecticut, USA.

出版信息

J Pharmacol Exp Ther. 1998 Jul;286(1):341-4.

PMID:9655878
Abstract

Daily subcutaneous administration of bovine parathyroid hormone (PTH)(1-34) stimulates bone formation and increases bone mass in rat tibiae, femora and lumbar spine. However, the effects of PTH on the whole body bone mineral content and density determined by dual energy x-ray absortiometry (DEXA) have not been previously reported in rats. Eighteen-month-old intact female rats were subcutaneously injected daily with 0, 40, 80 or 160 micrograms/kg/day of bovine PTH (1-34) for either 15 or 60 days. Whole body DEXA was performed at 1 day before autopsy, and bone area, bone mineral content (BMC) and bone mineral density (BMD) of the total body were determined. Total femoral, tibial and lumbar spine BMD was also determined ex vivo. Cancellous bone histomorphometry was performed on sections of double-labeled proximal tibial metaphyses. Whole body bone mineral content and density were significantly increased by 60 days, but not by 15 days, of PTH treatment at all dose groups compared with vehicle controls. Lumbar vertebral and total femoral BMD was significantly increased at all doses of PTH by 15 days of administration and further increased by 60 days. All doses of PTH increased trabecular bone area in proximal tibial metaphyses by 15 days and further increased by 60 days. All doses of PTH increased trabecular bone area in proximal tibial metaphyses by 15 days and further increased by 60 days. In proximal tibial cancellous bone, dose-dependent increases in percent labeled perimeter, mineral apposition rate and bone formation rate-bone volume referent were found between 40 and 160 micrograms/kg of PTH treatment by 15 days, and no further increases were found by 60 days. Our results showed that in aged female rats, bovine PTH(1-34) increased bone formation and total body bone mass.

摘要

每日皮下注射牛甲状旁腺激素(PTH)(1-34)可刺激大鼠胫骨、股骨和腰椎的骨形成并增加骨量。然而,甲状旁腺激素对通过双能X线吸收法(DEXA)测定的大鼠全身骨矿物质含量和密度的影响此前尚未见报道。对18月龄的未切除卵巢的雌性大鼠,每日皮下注射0、40、80或160微克/千克/天的牛PTH(1-34),持续15天或60天。在处死前1天进行全身DEXA检查,并测定全身的骨面积、骨矿物质含量(BMC)和骨矿物质密度(BMD)。还离体测定了股骨、胫骨和腰椎的总BMD。对双标记的近端胫骨 metaphyses切片进行松质骨组织形态计量学分析。与赋形剂对照组相比,所有剂量组的PTH治疗60天可显著增加全身骨矿物质含量和密度,但15天则无此作用。给药15天时,所有剂量的PTH均可显著增加腰椎和股骨总BMD,60天时进一步增加。所有剂量的PTH在15天时均可增加近端胫骨 metaphyses的小梁骨面积,60天时进一步增加。在近端胫骨松质骨中,15天时在40至160微克/千克的PTH治疗之间发现标记周长百分比、矿物质沉积率和骨形成率-骨体积参考值呈剂量依赖性增加,60天时未发现进一步增加。我们的结果表明,在老年雌性大鼠中,牛PTH(1-34)可增加骨形成和全身骨量。

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