Pharmacology Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
Pharmacology Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
Biomed Pharmacother. 2017 May;89:1115-1124. doi: 10.1016/j.biopha.2017.02.105. Epub 2017 Mar 12.
Epidemiological studies suggest a possible link between osteoporosis and cardiovascular diseases. Mevalonate pathway was pointed to as a part of this link. This study was done to investigate the effects of Alendronate (Al) and Simvastatin (Sim), both act on the mevalonate pathway, on osteoporosis, dyslipidemia and atherosclerotic changes in ovariectomized (OVX) rats fed high fat diet (HFD).
60 female albino rats were equally divided into 5 groups: control sham, OVX-HFD untreated, OVX -HFD treated with Al (3mg/kg/d) or/and Sim (6mg/kg/d). Treatments were taken for 4 weeks by oral gavage and were started 8 weeks after ovariectomy.
OVX-HFD untreated group exhibited a significant negative alteration in lipid profile and on different bone markers e.g. alkaline phosphatase, hydroxyproline and osteocalcin. A significant increase in body weights and on serum levels of TNFα, iNOS and leptin were also found compared to control sham group. Vascular reactivity studies revealed a significant decrease in effective concentration 50 of phenylephrine and in acetylcholine% of relaxation and a significant increase in maximum contractile response of phenylephrine. The atherosclerotic and osteoporotic changes were further confirmed histopathologically. Treatment of OVX-HFD with Al or/and Sim significantly improved these deleterious effects compared to OVX-HFD untreated group. Comparing the combination therapy versus the mono-therapy exhibited a significant improvement in different tested parameters which came in favor of the combination therapy.
Al and Sim have anti-osteoporotic, anti-dyslipidemic and anti-atherosclerotic beneficial effects. Their combination has more promising effects in treatment of osteoporosis, dyslipidemia and atherosclerosis.
流行病学研究表明，骨质疏松症与心血管疾病之间可能存在关联。甲羟戊酸途径被认为是这种关联的一部分。本研究旨在探讨阿仑膦酸钠（Al）和辛伐他汀（Sim），这两种药物均作用于甲羟戊酸途径，对高脂饮食喂养去卵巢（OVX）大鼠骨质疏松症、血脂异常和动脉粥样硬化变化的影响。
60 只雌性白化大鼠等分为 5 组：假手术对照组、OVX-HFD 未治疗组、OVX-HFD 用 Al（3mg/kg/d）或/和 Sim（6mg/kg/d）治疗组。通过口服灌胃给药，治疗持续 4 周，于去卵巢 8 周后开始。
OVX-HFD 未治疗组的血脂谱和不同骨标志物（如碱性磷酸酶、羟脯氨酸和骨钙素）发生显著负性改变。与假手术对照组相比，体重和血清 TNFα、iNOS 和瘦素水平也显著增加。血管反应性研究显示，苯肾上腺素的有效浓度 50 显著降低，乙酰胆碱的松弛百分比显著降低，苯肾上腺素的最大收缩反应显著增加。动脉粥样硬化和骨质疏松变化在组织病理学上进一步得到证实。与 OVX-HFD 未治疗组相比，用 Al 或/和 Sim 治疗 OVX-HFD 显著改善了这些有害影响。与单药治疗相比，联合治疗在不同测试参数上显示出显著改善，这有利于联合治疗。
Al 和 Sim 具有抗骨质疏松、抗血脂异常和抗动脉粥样硬化的有益作用。它们的联合治疗在骨质疏松症、血脂异常和动脉粥样硬化的治疗中具有更有前途的效果。
