SD大鼠骨性关节炎合并骨质疏松症模型的建立

背景：临床工作中发现，同时患有骨性关节炎和骨质疏松症患者占有相当大的比例，因此建立骨性关节炎+骨质疏松症疾病模型模拟临床中绝经妇女病变的基本特征，将为临床中更好的防治骨性关节炎、骨质疏松症提供帮助。目的：尝试建立骨性关节炎+骨质疏松症动物模型。设计、时间及地点：随机对照动物实验，细胞病理学观察，于2008-08/2009-01在新疆医科大学科研中心、新疆医科大学附属中医医院完成。材料：40只4月龄雌性SD大鼠，体质量(210±10) g，以抽签法随机分为正常对照组、骨性关节炎组、骨质疏松症组、骨性关节炎+骨质疏松症组。方法：骨性关节炎+骨质疏松症组先行背部两侧腰椎旁1.5 cm处纵行切口入腹，切除双侧卵巢，结扎卵巢动脉制作骨质疏松症模型。1个月后依次切开左膝关节皮肤、皮下组织、筋膜等，纵向切开关节囊，在直视下切断前交叉韧带，摘除半月板，依次缝合皮下组织和皮肤制作骨性关节炎模型，置于温暖环境，抗生素皮下注射3 d，并驱赶1个月。骨性关节炎组、骨质疏松症组分别按照上述方法制作骨性关节炎、骨质疏松症模型。正常对照组大鼠不作任何处理。主要观察指标：待大鼠6月龄时，取左膝股骨髁关节软骨做光镜、电镜观察，取左侧股骨测量股骨近端骨密度。结果：3组模型大鼠关节软骨变薄、退变，骨质疏松症组、骨性关节炎+骨质疏松症组骨小梁稀疏，排列紊乱，骨小梁及骨皮质松解。骨性关节炎组及骨性关节炎+骨质疏松症组切线层大部分缺失，移形层受损严重，细胞肥大，大量簇集，大量毛细血管侵入软骨下骨及钙化层，甚至突破潮线；骨质疏松症组可见关节软骨切线层变薄，并出现双重潮线。骨性关节炎及骨性关节炎+骨质疏松症组关节内髁部软骨细胞异形性增多，表现为细胞核形态不规则、细胞器减少，细胞核固缩，染色质分布不均匀，胞质内可见线粒体肿胀，粗面内质网扩张，胞浆内微丝堆积，可见脂滴和糖原颗粒，胶质纤维断裂，排列紊乱，大量软骨细胞凋亡。3组模型大鼠骨密度较正常对照组大鼠明显下降(P < 0.05)。结论：成功建立了骨性关节炎+骨质疏松症动物模型。

Establishment of SD rat models of osteoarthritis and osteoporosis

BACKGROUND: Clinical work shows that there are a large proportion of patients suffering from osteoarthritis (OA) and osteoporosis (OP), therefore establishing OA+OP models to simulate the clinical disease in postmenopausal women addressing the basic characteristics of lesions, will offer better prevention and treatment of OA+OP in clinical practice. OBJECTIVE: To attempt to create OA+OP animal model.DESIGN, TIME AND SETTING: Randomized controlled animal experiment in terms of cell pathology was performed between August 2008 and January 2009 in the Scientific Research Center and Traditional Chinese Medicine Hospital of Xinjiang Medical University. MATERIALS: Forty 4-month-old female SD rats, weighing (210±10) g, were randomly divided into normal control group, OA group, OP group, OA + OP group. METHODS: In the OA + OP group, rats underwent abdominal incision 1.5 cm longitudinal on both sides of lumbar spine on back, followed by bilateral ovarian resection and ovarian artery ligation, to establish OP models. One month after the skin incision, left knee skin, subcutaneous tissue and fascia were cut, then joint capsule was given a vertical incision. Anterior cruciate ligament was cut off in orthophoria, meniscus was removed, followed by subcutaneous tissue and skin suture, OA model was prepared and placed under warm environment, antibiotic subcutaneous injection for 3 days, and the displacement of one month. OA group and OP group were produced in accordance with the above method of OA, OP model. Normal control rats received no treatment. MAIN OUTCOME MEASURES: When the rats were 6 months old, the left knee femoral condyle articular cartilage were examined by light microscopy and electron microscopy, left femur was used to measure proximal femoral bone mineral density.RESULTS: In three groups of model rats, articular cartilage become thinning and degeneration. In the OP model group and OA + OP model group, trabecular was sparse and arranged in disorder. In the OA model group and OA + OP model group, the incision layer was chiefly deleted, transferring layer was greatly injured, cell hypertrophy and colony were observed, a large amount of blood capillary invaded into cartilage and calcification layer, even break through tidal line; in OP model group, incision layer of articular cartilage became thinning and appeared bilateral tidal line. In the OA model group and OA + OP model group, knee condylar number of special-shaped cartilage cells increased, manifested as irregular nuclei, reduced cell organelle, nuclear shrinkage, chromatin uneven distribution, mitochondrial swelling, rough expansion of endoplasmic reticulum, accumulation of cytoplasmic microfilaments, showing lipid droplets and glycogen granules, glial fibrillary fracture, disorder arrangement, a large number of cartilage cells were apoptotic. Three groups of model rats exhibited a dramatically decreased bone mineral density compared with control rats (P < 0.05). CONCLUSION: The animal model of OA + OP was successfully established.