SD大鼠骨代谢与非洛地平的干预

Effects of felodipine on bone metabolism in SD rats

目的:流行病学报告提示治疗心血管疾病的重要药物钙离子通道阻滞剂影响骨代谢,但这种作用与药物的剂量和作用时间的关系还不明确。观察不同剂量、不同时间的非洛地平对SD大鼠骨代谢的作用。方法:实验于2006-05/2007-04在西安交通大学动物实验中心完成。①实验分组:132只6月龄SD大鼠,随机分为4组:正常对照组,非洛地平0.15,0.45,1.25mg/kg组,每组33只。②实验方法:非洛地平各组每天按0.15mg/kg,0.45mg/kg,1.25mg/kg剂量灌胃非洛地平,正常对照组灌服等量生理盐水。③实验评估:在实验第3,4,5,6个月时每组随机取8只大鼠,对其股骨和腰椎骨密度、身长、体质量和血清游离钙、磷、碱性磷酸酶、胆固醇、三酰甘油含量进行测定。结果:进入结果分析的SD大鼠共有127只,正常对照组31只,非洛地平0.15mg/kg组31只,非洛地平0.45mg/kg组32只,非洛地平1.25mg/kg组33只。①各组大鼠股骨和腰椎骨密度:给药后6个月后非洛地平0.15mg/kg组大鼠的股骨和腰椎骨密度高于正常对照组(P<0.01),非洛地平0.45,1.25mg/kg组股骨骨密度则出现降低(P<0.01),非洛地平1.25mg/kg组降低更明显(P<0.01)。②各组大鼠的身长、体质量和血清钙、磷、碱性磷酸酶、胆固醇、三酰甘油含量:不同剂量的非洛地平组与正常对照组比较,差异无显著性。各时间段比较差异也无显著性。结论:①短期应用非洛地平对大鼠骨代谢无明显影响。②长期应用低剂量非洛地平对大鼠股骨和腰椎的骨代谢产生正性的影响。③长期应用中、高剂量非洛地平对大鼠负重骨(股骨)的骨代谢产生负性的影响,剂量越大,负性影响越明显;而对非负重骨(腰椎)的骨代谢无明显影响。

AIM： Epidemiological reports have suggested that calcium ion channel blocker, the important medicine for cardiovascular diseases, has influence on bone metabolism, however, whether it is related to the dose and duration of medicine is still uncertain. In this study, the effect of felodipine at different doses and different time on the bone substance metabolism of SD rats was investigated. METHODS： The experiment was conducted in the Animal Experimental Center of Xi＇an Jiaotong University from May 2006 to April 2007. ①132 six-month-old SD rats, half male and half female, were selected and randomly divided into four groups with 33 rats in each group. 0.15, 0.45 and 1.25 mg/kg felodipine groups were intragastrically infused with felodipine at corresponding dose; control group with matching normal saline. ②Eight rats of each group were randomly selected respectively at the 3^th, 4^th, 5^th and 6^th months. The femur and lumbar spine bone mineral density （BMD）, body length, body mass, and serum calcium （Ca）, phosphorus （P）, alkaline phosphatase （ALP）, cholesterol （CH） and triglyceride （TG） levels were measured. RESULTS： 127 rats entered the final result analysis including 31 of control group, 31 of 0.15 mg/kg felodipine group, 32 of 0.45 mg/kg group and 33 of 1.25 mg/kg group. After 6 months administration, the femur and lumbar spine BMD of 0.15 mg/kg felodipine group was higher than that in normal control group （P〈 0.01）, while the BMD of 0.45 and 1.25 mg/kg felodipine groups was decreased （P 〈 0.01）, especially 1.25 mg/kg group （P 〈 0.01）. ②There was no significant difference in the body length, body mass and serum Ca, P, ALP, CH, and TG between felodipine groups and control group. Meanwhile, no difference was found either at different time periods. CONCLUSION： ①Short-term application of felodipine has no obvious effect on bone metabolism in rats. ②Long-term application of low-dose felodipine has a positive impact on the bone metabolism of femur and lumbar spine. ③Long-term application of moderate and high dose felodipine shows negative effects on the femur （weight-bearing bone） dose dependently, but no significant effect on the bone metabolism of lumber which is non-weight-bearing bone in rats.