Department of Orthopedic, Beijing Army General Hospital, Dongcheng District, Nanmencang No. 5, Beijing, China.
Injury. 2011 Aug;42(8):825-32. doi: 10.1016/j.injury.2011.03.040. Epub 2011 May 4.
Chronic obstructive pulmonary disease (COPD) is at increased risk for developing osteoporosis (OP) with subsequent proximal femur fracture. The presence of COPD is suggested to be a strong risk factor for proximal femur fracture or hip fracture. However, what happen behind it is not clearly understood.
To investigate the pattern of cytokine (TNF-a, IL-6, and IL-10) releases in pulmonary and hepatic in rats with COPD suffering from proximal femur fracture, and its possible adverse effect on pulmonary and hepatic.
This paper has two parts. In the first part, we describe the procedure of COPD model in detail. In the second part, we study the influences of fracture on the COPD rats. 5 months WISTAR rats with 37 weeks cigarette smoking exposure (CS group) were dynamically determined for pulmonary function, inflammatory response in bronchoalveolar lavage fluid (BALF), histological changes in pulmonary in the first part. When the COPD model is proved to be successful, we begin the second part. COPD rats were euthanized at 2, 24, 48, 72, and 96h after proximal femur fracture (fracture group) or anaesthesia (control group). Cytokines (TNF-a, IL-6, and IL-10) and myeloperoxidase activity of pulmonary and hepatic (MPO) were measured with enzyme-liked immunosorbent assay technique. Permeability changes of the lung were assessed via bronchoalveolar lavage, and those of the liver via assessment of oedema formation. Tissues were further examined microscopically.
The current sidestream cigarette smoke induced rat COPD model has been proved an adequate animal model with several advantages as assessed by dynamically monitored lung mechanics and pathological changes for 37 weeks. In the second part, TNF-a, IL-6, and IL-10 levels of pulmonary tissue were significantly increased after proximal femur fracture compared to control rats. TNF-a, and IL-6 levels in pulmonary peaked at 2h, 24h in fracture group, whereas IL-10 level peaked at 24h and 96h. Pulmonary myeloperoxidase activity, permeability and histological score in fracture group were remarkably elevated, and peaked at 24h. In addition to TNF-a, all above parameters did not return to normal through our study. Hepatic in COPD rats showed notable increase of cytokines (TNF-a, IL-6, and IL-10), myeloperoxidase activity, histological score, and permeability in fracture group compared to control rats, and severity of these changes were much lower than in pulmonary. Apart from TNF-a, the peak of these parameters was at 24h after fracture. Changes of cytokines, MPO activity, permeability and histological score in pulmonary and hepatic in control rat were little changed.
COPD rats produced a remarkably increase of inflammatory response (TNF-a, IL-6, IL-10) in lung (liver) after proximal femur fracture, which lead to lung (liver) injury, as evidence by changes of MPO, permeability, and histological scores in local organs.
慢性阻塞性肺疾病（COPD）发生骨质疏松症（OP）和随后的股骨近端骨折的风险增加。COPD 的存在被认为是股骨近端骨折或髋部骨折的一个强烈危险因素。然而，其背后的机制尚不清楚。
探讨 COPD 大鼠股骨近端骨折后肺部和肝脏细胞因子（TNF-a、IL-6 和 IL-10）释放的模式及其对肺部和肝脏可能产生的不良影响。
本文分为两部分。第一部分详细描述了 COPD 模型的建立过程。第二部分研究了骨折对 COPD 大鼠的影响。37 周香烟暴露（CS 组）的 WISTAR 大鼠 5 个月，动态测定肺功能、支气管肺泡灌洗液（BALF）中的炎症反应、第一部分中肺组织的组织学变化。当 COPD 模型被证明成功后，我们开始第二部分。股骨近端骨折（骨折组）或麻醉（对照组）后 2、24、48、72 和 96 小时处死 COPD 大鼠。采用酶联免疫吸附试验技术测定肺和肝组织中的细胞因子（TNF-a、IL-6 和 IL-10）和髓过氧化物酶活性（MPO）。通过支气管肺泡灌洗评估肺通透性变化，通过评估水肿形成评估肝通透性变化。进一步对组织进行显微镜检查。
目前的侧流香烟烟雾诱导的大鼠 COPD 模型已被证明是一种合适的动物模型，通过 37 周的动态监测肺力学和病理变化进行了评估。在第二部分中，与对照组大鼠相比，股骨近端骨折后肺组织中的 TNF-a、IL-6 和 IL-10 水平显著升高。TNF-a 和 IL-6 水平在骨折组中于 2 小时和 24 小时达到峰值，而 IL-10 水平在 24 小时和 96 小时达到峰值。骨折组肺组织 MPO 活性、通透性和组织学评分显著升高，并于 24 小时达到峰值。除 TNF-a 外，所有上述参数在我们的研究中均未恢复正常。与对照组大鼠相比，COPD 大鼠的肝组织中细胞因子（TNF-a、IL-6 和 IL-10）、MPO 活性、组织学评分和通透性均有明显升高，且这些变化的严重程度明显低于肺组织。除 TNF-a 外，这些参数的峰值出现在骨折后 24 小时。对照组大鼠肺和肝组织中细胞因子、MPO 活性、通透性和组织学评分的变化均较小。
COPD 大鼠股骨近端骨折后肺部（肝脏）炎症反应（TNF-a、IL-6、IL-10）明显增加，导致肺部（肝脏）损伤，局部器官 MPO、通透性和组织学评分的变化证实了这一点。
