补肾通络方对SD大鼠骨性关节炎、骨质疏松症及骨性关节炎并骨质疏松症模型骨密度的影响

Effect of Bushen Tongluo Fang on bone mineral density of SD rats with osteoarthritis, osteoporosis or osteoarthritis with osteoporosis

背景:临床上发现通过补肾通络方治疗骨性关节炎及骨质疏松症有良好的临床疗效。目的:尝试建立骨性关节炎+骨质疏松症动物模型,观察补肾通络方对SD大鼠骨性关节炎、骨质疏松症及骨性关节炎+骨质疏松症模型骨密度的影响。设计、时间及地点:随机对照观察实验,于2008-08/2009-01在新疆医科大学科研中心完成。材料:4月龄雌性SD大鼠70只,随机分为正常对照组、骨性关节炎组、骨性关节炎+补肾通络方组、骨质疏松症组、骨质疏松症+补肾通络方组、骨性关节炎+骨质疏松症组、骨性关节炎+骨质疏松症+补肾通络方组,每组10只。补肾通络方由骨碎补、杜仲、山萸肉、熟地黄、补骨脂、秦艽、寄生、独活、桃仁、红花、当归、川芎、白芍等组成。方法:取20只大鼠,采用改良Hulth法制作骨性关节炎模型,选择10只于术后1个月灌胃给予补肾通络方;取20只大鼠,采用去势法制作骨质疏松症模型,选择10只于术后1个月灌胃给予补肾通络方;取20只大鼠按上述方式同时制作骨性关节炎、骨质疏松症模型,选择10只于术后1个月灌胃给予补肾通络方。按大鼠体质量灌胃给药,根据人鼠换算出服药量为10.31mg/(kg·d),2次/d,连续4周。正常对照组不做任何处理。主要观察指标:电镜、光镜观察大鼠左侧股骨内髁关节软骨组织形态学变化,双能X射线观察大鼠左侧股骨骨密度变化。结果:光镜下观察3组模型大鼠骨小梁局部区域变细,排列较紊乱,纵向结构受到破坏,连续性较差,出现较多的断裂点,关节软骨变薄、退变;电镜下观察3组模型大鼠模型组大鼠关节软骨细胞异形性增多,表现为细胞核形态不规则,细胞壁断裂不完整,细胞器减少,细胞核固缩,染色质分布不均匀,并有大量软骨细胞凋亡。骨性关节炎组、骨质疏松症组、骨性关节炎+骨质疏松症组大鼠骨密度较正常对照组明显下降(P<0.05),经补肾通络方干预后骨密度上升(P<0.05)。结论:补肾通络方对骨性关节炎、骨质疏松症SD大鼠骨密度有上调作用,但其有效作用机制尚需进一步研究探讨。

BACKGROUND： The clinical trials found Bushen Tongluo Fang （BSTLF） is effective for treatment of osteoarthritis （OA） and osteoporosis （OP）. OBJECTIVE： To create OA ＋ OP animal models and to observe the effect of BSTLF on bone mineral density of SD rats with OA, OP, or with OA ＋ OP. DESIGN, TIME AND SETTING： Randomized control experiment was performed in the Xinjiang Medical University research center between August 2008 and January 2009. MATERIALS： Seventy 4-month-old female SD rats were randomly divided into blank group, OA group, OA ＋ BSTLF group, OP group, OP ＋ BSTLF group, OA ＋ OP group, and OA ＋ OP ＋ BSTLF group. Each group contained 10 rats. BSTLF consisted of drynaria, eucommia bark, cornus officinalis, prepared rehmannia root, psoralen, gentiana, parasitic, doubleteeth pubesscent angelica root, peach kernel, safflower, Chinese angelica, szechwan lovage rhizome, Radix Paeoniae Alba, etc. METHODS： Twenty rats were induced OA model using Hulth method, 10 of them were selected to receive intragastric administration of BSTLF at one month postoperation; 20 rats were induced OP model using castration method, 10 of them were selected to receive intragastric administration of BSTLF at one month postoperation; 20 rats were induced OA ＋ OP in accordance with the above-mentioned procedures, and 10 of them were selected to receive intragastric administration of BSTLF at one month postoperation. According to rat body mass, the administration dose was determined as 10.31 mg/kg, 2 times per day. No treatment was given in normal control group. MAIN OUTCOME MEASURES： Morphological changes of rat left femoral condylar articular cartilage were detected with electron microscopy and light microscopy, dual-energy X-ray was used to observe the bone mineral density of rat left femur. RESULTS： Light microscope results showed three groups of rat bone trabecula became sparse, arranged in disorder, vertical structure was destroyed, present with poor continuity and more breakages, articular cartilage became thin and degenerated; electron microscopy showed that, rats of model group shaped articular cartilage of growing cell heteromorphism, showed irregular nuclei, incomplete cell wall fracture, reduced organelle and nuclear shrinkage, the chromatin was unevenly distributed, and a large number of cartilage cells died. Compared with normal control group, the OA group, OP group, OA ＋ OP group of SD rats showed a significantly decreased bone mineral density （P 〈 0.05）, which was increased after BSTLF administration （P 〈 0.05）. CONCLUSION： BSTLF can upregulate the bone mineral density in the SD rats with OA and OP, but its effective mechanism requires further study.