Karakus Emre, Halici Zekai, Albayrak Abdulmecit, Bayir Yasin, Demirci Elif, Aydin Ali, Ozturk-Karagoz Berna, Cadirci Elif, Ayan Arif Kursat, Sahin Ali, Unal Deniz
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum, Turkey.
Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
Inflammation. 2016 Feb;39(1):336-346. doi: 10.1007/s10753-015-0254-6.
This study was performed to evaluate the possible protective effect of two calcium channel blocker's "lacidipine (LAC) and amlodipine (AML)" on bone metabolism in an experimental ovariectomized and inflammation-induced osteoporosis rat model (OVXinf). For the purpose of this study, the rats were divided into eight groups, each containing eight rats: sham-operated control (group 1, SH), sham + inflammation (group 2, SHinf), ovariectomy (group 3, OVX), ovariectomy + inflammation (group 4, OVXinf), ovariectomy + LAC 4 mg/kg (group 5, OVX + LAC), ovariectomy + inflammation + LAC 4 mg/kg (group 6, OVXinf + LAC), ovariectomy + AML 5 mg/kg (group 7, OVX + AML), ovariectomy + inflammation + AML 5 mg/kg (group 8, OVXinf + AML). The levels of osteocalcin and osteopontin decreased in OVXinf + LAC and OVXinf + AML groups. The serum levels of TNF-α, IL-1β, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. Gene expression levels of the osteogenic factor runt-related transcription factor 2 (Runx2) and type I collagen 1A1 (Col1A1) significantly decreased in the OVXinf group, when compared with the control group. AML or LAC administrations increased the levels of Runx2 and Col1A1. These results suggest that amlodipine and lacidipine may be a novel therapeutic target for radical osteoporosis treatment in hypertensive patients.
本研究旨在评估两种钙通道阻滞剂“拉西地平（LAC）和氨氯地平（AML）”对实验性卵巢切除和炎症诱导的骨质疏松大鼠模型（OVXinf）骨代谢的可能保护作用。为了本研究的目的，将大鼠分为八组，每组八只：假手术对照组（第1组，SH）、假手术+炎症组（第2组，SHinf）、卵巢切除组（第3组，OVX）、卵巢切除+炎症组（第4组，OVXinf）、卵巢切除+4mg/kg拉西地平组（第5组，OVX+LAC）、卵巢切除+炎症+4mg/kg拉西地平组（第6组，OVXinf+LAC）、卵巢切除+5mg/kg氨氯地平组（第7组，OVX+AML）、卵巢切除+炎症+5mg/kg氨氯地平组（第8组，OVXinf+AML）。OVXinf+LAC组和OVXinf+AML组骨钙素和骨桥蛋白水平降低。与SH组相比，OVXinf大鼠血清TNF-α、IL-1β和IL-6水平显著升高。与对照组相比，OVXinf组成骨因子 runt相关转录因子2（Runx2）和I型胶原1A1（Col1A1）的基因表达水平显著降低。给予AML或LAC可提高Runx2和Col1A1的水平。这些结果表明，氨氯地平和拉西地平可能是高血压患者根治性骨质疏松治疗的新靶点。
