复方丹参制剂对糖皮质激素性骨质疏松症大鼠的防治作用(英文)

Preventive effects of compound danshen on glucocorticoid-induced osteoporosis in rats

背景:糖皮质激素长期大剂量应用可导致骨质丢失甚至股骨头坏死,是药源性骨损害的原因之一,对其干预研究具有实际意义。目的:探讨长期超生理剂量应用糖皮质激素对大鼠所致的骨质疏松症特点,同时观察中药复方丹参制剂的干预效应。设计:以实验动物为研究对象的随机对照实验研究。单位:一所医学院的实验动物中心、中心实验室和药理研究室。材料:实验于2002/2003在广东医学院实验动物中心、药理研究室和中心实验室完成。选用40只SD大鼠。方法:SD大鼠予泼尼松按2.7mg/kg每天灌胃,连续12周,同时予复方丹参制剂(丹参、黄芪、白术和淫羊藿)按2.5g/(kg·d),5.0g/(kg·d)和10.0g/(kg·d)进行治疗。实验结束后通过测量不脱钙胫骨上段的骨生长的静态和动态指标、尺骨中羟脯胺酸、钙磷含量以及股骨长度来观察糖皮质激素长期超生理剂量应用后对大鼠骨代谢的影响,并观察复方丹参制剂对其的防治作用。主要观察指标:主要结局:复方丹参制剂对泼尼松大鼠骨形态计量学静态、动态参数指标的影响;次要结局:复方丹参制剂对泼尼松大鼠骨生化指标及股骨物理指标影响的比较。结果:泼尼松大鼠质量明显下降P<0.01),骨形态学指标显示骨小梁(数量犤(1.98±0.20)/mm犦和骨小梁面积百分数(8.83%±0.98%)显著减少,骨表面骨形成率。

BACKGROUND:Long term large dose application of glucocorticoid can cause osseous loss and even femoral head necrosis, which is one of the reasons of pharmaceutical damages.Researches on its intervention have practical significance.OBJECTIVE:To study the osteoporosis induced by long term large dose administration of glucocorticoid,and investigate the preventive effects of compound danshen(CD) in male rats. DESIGN:A randomized and controlled study by employing experimental animals as subjectsSETTING:An Experimental Animal Center,a Central Laboratory and an Institute of Pharmacology of a Medical CollegePARTICIPANTS:The study was conducted in the Experimental Animal Center,the Central Laboratory and the Institute of Pharmacology of Guangdong Medical College between 2002 and 2003.Totally 40 SD rats were employed.INTERVENTION:SD rats were treated with prednisone(2.7 mg/kg per day) by oral gavages and CD including danshen huangqi , baishu and yinyanghuo at dose of 2.5 g/kg per day,5.0 g/kg per day or 10.0 g/kg per day respectively,once a day for 12 weeks.At the experimental endpoint,the impacts of long term large dose (beyond physiologic dose) application of glucocorticoid on bone metabolism and the preventive effects of CD were observed through the measurement of the static and dynamic indicators for bone growth in un decalcified superior tibia,the detection of Ca2+ and hydroxyproline contents in ulna,and the length and width of thighbone. MAIN OUTCOME MEASURES:Principal consequences:the impacts of CD on quantitative static and dynamic parameters of osseous morphology in rats with prednisone induced osteoporosis;Secondary consequences:the comparison of the impacts of CD on bone biochemical indictors and femoral physical indicators in rats with prednisone induced osteoporosis.RESULTS:In glucocorticoid control group(GC group),bone mass significantly decreased(P< 0.01);as indicated by bone morphological indicators,the number of bone trabecula [(1.98± 0.20) / mm]and the percentage of bone trabecular size [(8.83± 0.98) % ] significantly reduced;the ratio of osteogenesis rate at bone surface (8.91± 3.97)/neogenesis bone trabacular size to total bone trabecular size(332.8± 142.5)/neogenesis bone trabecular size to bone size(29.6± 13.2) significantly decreased;bone absorption perimeter significantly increased(P< 0.01);osseous content in ulna reduced[(0.155± 0.01) g];and femoral length[(32.64± 0.51) mm]significantly shortened(P< 0.05).But in CD group, CD had certain preventive effects on bone injury induced by prednisone while there was no significant difference among each subgroup with different dose.CONCLUSION:Long term application of prednisone can significantly inhibit bone growth and induce bone loss.CD has favorable preventive effects on bone loss through its promotion of osteogenesis and inhibition of osteoclast bone resorption.