1Department of Orthopedics, Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Dongmen North Road 1017, Luohu District, Shenzhen, 518020 China.
2Department of Radiology, Second Clinical Medical College of Jinan University (Shenzhen People's Hospital), Shenzhen, 518020 China.
Cell Mol Biol Lett. 2018 Oct 1;23:47. doi: 10.1186/s11658-018-0114-0. eCollection 2018.
Evidence has shown that endogenous HS plays an important role in the physiological and pathophysiological processes of many organs. The study aimed to explore whether exogenous HS has a potential therapeutic effect on a rat ovariectomy-induced model of osteoporosis.
The OVX osteoporosis model was established in female Sprague-Dawley rats by full bilateral ovariectomy. The rats were randomly divided into four groups, with the two experimental groups receiving an intraperitoneal injection of GYY4137 or sodium alendronate. The level of HS in the plasma was determined and common laboratory indicators to diagnose osteoporosis, such as alkaline phosphatase (ALP) activity and the levels of osteocalcin (OCN), calcitonin, parathyroid hormone and leptin were measured. The bone mineral density (BMD) of the 4th and 5th lumbar vertebrae was measured using dual-energy X-ray absorptiometry. The maximum stress of femoral fracture was obtained through a three-point bending test of the femur.
The OVX osteoporosis model was successfully established. GYY4137 was injected to increase the level of HS in the plasma in one group, designated OVX-GYY during the observation period ( < 0.05). At 12 weeks, the BMD value of the fourth lumbar vertebra in the OVX-GYY group had increased ( < 0.05). The BMD femur value in the OVX-vehicle group had decreased ( < 0.05). Bilateral ovariectomy leads to biochemical disorders related to bone metabolism and hormone levels in rat plasma (all < 0.05). Ovariectomy also reduced blood calcium, blood phosphate and calcitonin, and increased parathyroid hormone and leptin. The opposite results were obtained for the groups with alendronate sodium or GYY4137 treatment (all < 0.05).
Through the slow release of HS, GYY4137 did an excellent job of simulating endogenous neuroendocrine gaseous signaling molecules. Exogenous HS had a regulatory effect on osteoporosis in ovariectomized rats, showing potential value for the treatment of human postmenopausal osteoporosis.
有证据表明，内源性 HS 在许多器官的生理和病理生理过程中发挥着重要作用。本研究旨在探讨外源性 HS 对去卵巢大鼠骨质疏松模型是否具有潜在的治疗作用。
通过双侧卵巢切除术建立雌性 Sprague-Dawley 大鼠去卵巢骨质疏松模型。将大鼠随机分为 4 组，其中 2 个实验组分别接受 GYY4137 或阿仑膦酸钠腹腔注射。测定血浆 HS 水平，测定碱性磷酸酶（ALP）活性及骨钙素（OCN）、降钙素、甲状旁腺激素和瘦素等诊断骨质疏松的常用实验室指标，采用双能 X 线吸收法测量第 4、5 腰椎骨密度（BMD），通过股骨三点弯曲试验获得股骨最大骨折应力。
成功建立了去卵巢骨质疏松模型。在观察期间，向一组大鼠注射 GYY4137 以增加血浆中 HS 的水平，命名为 OVX-GYY（<0.05）。12 周时，OVX-GYY 组第 4 腰椎 BMD 值增加（<0.05）。OVX-vehicle 组股骨 BMD 值降低（<0.05）。双侧卵巢切除导致大鼠血浆骨代谢和激素水平的生化紊乱（均<0.05）。卵巢切除还降低了血钙、血磷和降钙素，增加了甲状旁腺激素和瘦素。阿仑膦酸钠或 GYY4137 治疗组则得到了相反的结果（均<0.05）。
GYY4137 通过 HS 的缓慢释放，很好地模拟了内源性神经内分泌气体信号分子。外源性 HS 对去卵巢大鼠骨质疏松具有调节作用，具有治疗绝经后骨质疏松症的潜在价值。
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