School of Pharmacy, Nantong University, Nantong, China.
School of Medical Instrument and Food Engineering, University of Shanghai for Science and Technology, Shanghai, China.
Pharmacol Rep. 2018 Aug;70(4):705-711. doi: 10.1016/j.pharep.2018.02.008. Epub 2018 Feb 7.
This study aimed to study the osteo-preservative effects of captopril, an inhibitor on angiotensin-converting enzyme (ACE), on bone mass, micro-architecture and histomorphology as well as the modulation of captopril on skeletal renin-angiotensin system (RAS) and regulators for bone metabolism in mice with bilateral orchidectomy.
The orchidectomized (ORX) mice were orally administered with vehicle or captopril at low dose (10mg/kg) and high dose (50mg/kg) for six weeks. The distal femoral end, the proximal tibial head and the lumbar vertebra (LV) were stained by hematoxylin and eosin, Safranin O/Fast Green and masson-trichrome. Micro-computed tomography was performed to measure bone mineral density (BMD).
Treatment with captopril increased trabecular bone area at distal metaphysis of femur, proximal metaphysis of tibia and LV-4, moreover, high dose of captopril significantly elevated trabecular BMD of LV-2 and LV-5. The mRNA expressions of renin receptor, angiotensinogen, carbonic anhydrase II, matrix metalloproteinase-9, and tumor necrosis factor-alpha were significantly decreased in tibia of ORX mice following treatment with captopril. The administration with captopril enhanced the ratio of OPG/RANKL mRNA expression, the mRNA expression of transforming growth factor-beta and the protein expression of bradykinin receptor-1.
The inhibition on ACE by captopril exerts beneficial effects on trabecular bone of ORX mice. The therapeutic efficacy may be attributed to the regulation of captopril on local RAS and cytokines in bone.
本研究旨在探讨血管紧张素转换酶（ACE）抑制剂卡托普利对去势小鼠骨量、微结构和组织形态学的骨保护作用，以及卡托普利对去势小鼠骨骼肾素-血管紧张素系统（RAS）和骨代谢调节剂的调节作用。
将去势（ORX）小鼠口服给予载体或低剂量（10mg/kg）和高剂量（50mg/kg）卡托普利 6 周。用苏木精和伊红、番红 O/快绿和 Masson 三色染色染色股骨远端、胫骨近端头部和腰椎（LV）。采用微计算机断层扫描（micro-CT）测量骨密度（BMD）。
卡托普利治疗增加了股骨远端、胫骨近端和 LV-4 的小梁骨面积，此外，高剂量卡托普利显著提高了 LV-2 和 LV-5 的小梁骨 BMD。卡托普利治疗后，ORX 小鼠胫骨中肾素受体、血管紧张素原、碳酸酐酶 II、基质金属蛋白酶-9 和肿瘤坏死因子-α的 mRNA 表达显著降低。卡托普利增强了 OPG/RANKL mRNA 表达、转化生长因子-β的 mRNA 表达和缓激肽受体-1 的蛋白表达。
卡托普利抑制 ACE 对去势小鼠的小梁骨有有益的作用。治疗效果可能归因于卡托普利对骨局部 RAS 和细胞因子的调节作用。
