羊胫骨慢性骨髓炎模型的构建及评价

Construction and evaluation of a model of chronic osteomyelitis in sheep tibia

背景:高原环境会影响骨髓炎患者的免疫功能和代谢状态,导致疾病进程的加速或复杂化。构建有效稳定的慢性骨髓炎动物模型对于慢性骨髓炎的实验研究至关重要。目的:在高原地区建立一种基于羊的慢性骨髓炎模型,以供毒性评估和治疗性研究。方法:15只健康绵羊,将鱼肝油酸钠和金黄色葡萄球菌悬液注射至左侧胫骨中段髓腔内建立慢性骨髓炎模型,采用大体观察、体质量及体温监测、血液感染指标检测、影像学评分及微生物培养等方法进行评估与分析。结果与结论:①造模后所有绵羊在早期均可观察到局部组织肿胀和病腿跛行症状,伴有不同程度的食欲减退现象;造模1周后绵羊体质量出现轻微下降,体温未见明显变化。②造模4 d后红细胞沉降率明显加快(P<0.05),1个月后逐渐恢复正常水平;造模后4 d内白细胞数量出现明显升高的趋势,1周后恢复到正常状态;造模后C-反应蛋白水平明显增加(P<0.05),至实验结束仍显著高于正常水平(P<0.05)。③15只绵羊均有典型骨髓炎的放射学表现,溶骨性病灶的边界模糊不清且形态不规则,呈现出一种低密度透亮区域,其中夹杂着密度增高且分布不均的坏死骨块影像,病变区域皮质骨部分出现了不同程度的骨膜反应现象。④13只绵羊培养出单一金黄色葡萄球菌,另2只绵羊培养出金黄色葡萄球菌和大肠杆菌。提示通过向绵羊胫骨骨髓腔内注入适量的金黄色葡萄球菌菌液,并结合局部植入异物棉线与鱼肝油酸钠,可在高原地区成功构建一种可靠的绵羊胫骨慢性骨髓炎动物模型。

BACKGROUND:The plateau environment affects the immune function and metabolic status of patients with osteomyelitis,leading to acceleration or complication of the disease process.The construction of effective and stable animal models of chronic osteomyelitis is essential for experimental studies of chronic osteomyelitis.OBJECTIVE:To establish a sheep model of chronic osteomyelitis in plateau regions for toxicity assessment and therapeutic research.METHODS:Fifteen healthy sheep were selected in this study.Sodium morrhuate and Staphylococcus aureus suspension were injected into the medullary cavity of the middle segment of the tibia to establish the chronic osteomyelitis model.General observation,body mass and temperature monitoring,blood infection index detection,radiological scoring,and microbial culture were performed for evaluation and analysis.RESULTS AND CONCLUSION:(1)Local tissue swelling and lameness of the affected leg were observed in all sheep in the early stage after modeling,accompanied by varying degrees of anorexia.A slight decrease in body mass was observed in sheep 1 week after modeling,while no significant changes in body temperature were observed.(2)The erythrocyte sedimentation rate significantly accelerated 4 days after modeling(P<0.05)and gradually returned to normal levels after 1 month.The white blood cell count showed a significant increase within 4 days after modeling and returned to normal after 1 week.The level of C-reactive protein increased significantly after modeling(P<0.05)and remained significantly higher than normal until the end of the experiment(P<0.05).(3)Fifteen sheep exhibited typical radiological manifestations of osteomyelitis,including unclear boundaries,irregular osteolytic lesions,and low-density bright absorption areas with interspersed necrotic bone fragments of increased and uneven density.Different degrees of periosteal reaction were observed in the cortex near the lesion.(4)Thirteen sheep were cultured for a single strain of Staphylococcus aureus,while two sheep were cultured for Staphylococcus aureus and Escherichia coli.These findings indicate that a reliable chronic osteomyelitis animal model of sheep tibia can be successfully established in plateau regions by injecting an appropriate amount of Staphylococcus aureus suspension into the medullary cavity of sheep,combined with local implantation of foreign cotton thread and sodium morrhuate.