非洛地平对SD大鼠骨组织形态学的影响(一)

详细内容

作者：宋金辉，陈军，王伟卓，邹春雨，阎宏伟，王坤正

【摘要】 目的 明确非洛地平灌胃对SD大鼠骨质代谢的作用，确定其对骨质疏松的影响，为临床用药提供直接的动物实验证据。方法 SD大鼠132只，随机分为对照组及非洛地平高、中、底剂量组。对照组每天给予蒸馏水灌胃，非洛地平高、中、低剂量组分别每天给予非洛地平0.15、0.45、1.25mg/kg体重灌胃。3、4、5、6月后进行右侧股骨全长HE染色，计算平均骨小梁密度(MTPD)、平均骨小梁间距(MTPS)、平均骨小梁厚度(MTPT)、骨小梁间连接点数(TB.n)、骨小梁末端数(FFT)等静态参数。结果 ①3、4个月后，各组大鼠以上指标均无明显差异(P>0.05)；②5个月后，非洛地平高、中剂量组与正常对照组和低剂量组相比MTPD、MTPT、TB.n明显减低(P0.05)，MTPS、FFT则明显增加(P0.05)；③6个月后，非洛地平低剂量组与其他组相比，MTPD、MTPT、TB.n均明显增加(P0.05)，MTPS、FFT明显减少(P0.05)；而非洛地平高、中剂量组相比正常组，MTPD、MTPT、TB.n均明显减少(P0.05)，MTPS、FFT明显增大，高剂量组尤甚(P0.05，P0.01)。结论 非洛地平短期应用对大鼠股骨组织学结构无影响。随着用药时间的延长，中、高剂量能引起骨丢失；低剂量则能抑制骨吸收，利于向增加骨强度的方向发展，有效地保护骨骼。

【关键词】 非洛地平；骨组织形态学；大鼠；骨质代谢；骨质疏松

ABSTRACT: Objective To investigate the effects of felodipine on sclerotin metabolism of SD rats through intragastric administration and ascertain its effect on osteoporosis in order to afford animal experiment evidence for clinic. Methods The 132 SD rats were randomly divided into control group, felodipine high?dose group, medium?dose group, and low?dose group. The groups of high, medium and low dose were intragastrically administered with felodipine 0.15mg/kg, 0.45mg/kg and 1.25mg/kg, separately. The control group was intragastrically administered with distilled water. Total length of the rats? right lateral thigh was dyed with HE; the average bone trabecula density (MTPD), distance (MTPS), average bone trabecula thickness (MTPT), average bone trabecula conjunction number (TB.n) and average bone trabecula termination were calculated in 3, 4, 5, 6 months. Results ① Insignificant difference was found among the groups after 3, 4 months (P>0.05). ② Five months later, MTPD, MTPT and TB.n were found significantly lower in felodipine high? and medium?dose groups than in low?dose group (P0.05). However, MTPS and FFT increased significantly(P0.05). ③ Six months later, MTPD, MTPT and TB.n were found increased significantly in felodipine low?dose group than in the others (P0.05), but MTPS and FFT decreased significantly (P0.05). The results of MTPD, MTPT and TB.n were found decreased while MTPS and FFT were found increased significantly in felodipine high? and medium?dose groups pared with those in control group (P0.05), especially in high?dose group. Conclusion No significant effect on rat bone microarchitecture was found in felodipine short?term administration. Using felodipine of high or medium dose can result in bone loss with the time extension. Low?dose felodipine can inhibit bone absorption, increase bone strength, and protect the skeleton.

KEY WORDS: felodipine; bone histomorphology; rat; sclerotin metabolism; osteoporosis

近年来，中老年人因为钙丢失引起的骨质疏松已经引起人们广泛的重视，而许多老年人因合并心脑血管病，常需长期服用钙离子通道阻滞剂(calcium channel blocker, B)。B能选择性地阻滞钙离子经细胞膜上电压依赖性钙通道进人细胞内，减少胞内钙离子浓度，从而影响细胞的功能。钙离子是细胞整合、运动的第二信使，广泛影响体内的生理和病理过程。由于B的药理作用涉及钙代谢，因而必然影响骨钙代谢，临床广泛使用B对正常骨骼的影响以及导致骨质疏松的可能性已引起人们的关注。本研究探讨非洛地平灌胃对SD大鼠骨质代谢的作用，确定其对骨质疏松的影响，为临床用药提供直接的动物实验证据。

1 材料与方法

1.1 实验动物 SD大鼠132只，6月龄，普通级，体重277～310g，平均286.4g，雌雄各半，由西安交通大学医学院实验动物中心提供，合格证号：陕医动证字2006105号。

1.2 药品及仪器 非洛地平片(2.5mg/片)，商品名：联环尔定，批号：20060302，江苏联环药业股份有限公司产品。病理图像分析仪：德国LEICA公司Q550CW全自动图像分析系统，由西安交通大学医学院实验中心共聚焦显微镜室提供。