Department of Biochemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
Department of Internal Medicine, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
J Pharm Pharmacol. 2021 Dec 7;73(12):1693-1702. doi: 10.1093/jpp/rgab123.
Our aim is to explain the relationship between Ang II and Scl in osteoporotic (OP) rats and the contribution of Scl in the antiosteoporotic effect mechanism of angiotensin receptor blockers (ARB).
This study consists of two sub-studies conducted on 4th and 12th weeks after ovariectomy. In study 1, treatment was started immediately after bilateral ovariectomy (OVX), while, in study 2, treatment was started 2 months after OVX. Two different doses of telmisartan (5 and 10 mg/kg) were administered with the aid of gavage for 30 days in both sub-study groups.
Serum and tissue Scl, osteocalcin, osteopontin and tartrate-resistant acid phosphatase mRNA expressions were higher and bone mineral densities (BMD) and bone-specific alkaline phosphatase (BALP) mRNA expressions were found to be lower in the OVX groups compared with the sham group. In OVX groups where two different doses of telmisartan were administered, BMD and BALP mRNA expressions increased and serum and tissue Scl decreased.
There may be a close relationship between angiotensin II and sclerostin in the development of osteoporosis. In this study, telmisartan administration showed an antiosteoporotic effect and significantly decreased the level of sclerostin. These results strongly support this relationship.
本研究旨在解释骨质疏松症（OP）大鼠中 Ang II 与 Scl 之间的关系以及 Scl 在血管紧张素受体阻滞剂（ARB）抗骨质疏松作用机制中的作用。
本研究包括 4 周和 12 周卵巢切除后的两个子研究。在研究 1 中，双侧卵巢切除（OVX）后立即开始治疗，而在研究 2 中，OVX 后 2 个月开始治疗。两个不同剂量的替米沙坦（5 和 10 mg/kg）通过灌胃在两个子研究组中给药 30 天。
与假手术组相比，OVX 组的血清和组织 Scl、骨钙素、骨桥蛋白和耐酒石酸酸性磷酸酶 mRNA 表达升高，骨密度（BMD）和骨特异性碱性磷酸酶（BALP）mRNA 表达降低。在给予两种不同剂量替米沙坦的 OVX 组中，BMD 和 BALP mRNA 表达增加，血清和组织 Scl 降低。
血管紧张素 II 和 Scl 在骨质疏松症的发生发展中可能存在密切关系。在这项研究中，替米沙坦的给药表现出抗骨质疏松作用，并显著降低了 Scl 的水平。这些结果有力地支持了这种关系。
