Development of osteoarthritis in the knee joints of Wistar rats after strenuous running exercise in a running wheel by intracranial self-stimulation
Development of osteoarthritis in the knee joints of Wistar rats after strenuous running exercise in a running wheel by intracranial self-stimulation
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DOI：
10.1016/s0344-0338(98)80010-1
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发表时间：
1998-01-01
影响因子：
2.8
通讯作者：
Neumann, W
中科院分区：
文献类型：
--
作者：
Pap, G;Eberhardt, R;Neumann, W
为探讨过度运动负荷对雄性Wistar大鼠膝关节骨关节炎(OA)形成的影响。Wistar大鼠每天跑500 m，每周5天，在转轮上进行颅脑自我刺激跑步运动。据此，10只大鼠在3周内跑了15公里，另外10只大鼠在6周内总共跑了30公里。未进行跑步训练的Wistar大鼠13只作为对照。所有大鼠的完整膝关节切片均采用Mankins分级系统进行组织学评估，并将结果分为非、轻、中、重度骨性关节炎。此外，通过免疫组织化学染色检测软骨细胞对基质金属蛋白酶-3的免疫反应性。膝关节切片的组织学评价显示，随着运动负荷的增加，骨关节炎的改变明显增加。而在跑15公里的大鼠中，除了两个膝关节外，所有的大鼠都显示出轻度的骨关节炎，而在跑30公里的大鼠中，中度的骨关节炎是主要的发现。相比之下，对照组中未发现骨性关节炎。基质金属蛋白酶-3的免疫染色显示，随着运动负荷的增加，软骨细胞对基质金属蛋白酶-3的免疫反应性显著增强，这表明在运动负荷增加的过程中，这种软骨降解酶的产生是依赖于负荷的。与对照组的47.4%的软骨细胞对基质金属蛋白酶-3的免疫反应相比，在15公里跑的大鼠中，这一比例上升到70.4%，在30公里跑的大鼠中甚至高达89.9%。总而言之，在Wistar大鼠中，过度的跑步负荷会导致显著的、与跑步距离相关的骨关节改变，这至少部分是由于随着跑步距离的增加，基质金属蛋白酶-3的产生增加所致。在这个运动模型中，颅内自我刺激是激发Wistar大鼠在转轮上过度跑的一种有效方法。这一模型为研究办公自动化发展的不同过程提供了广泛的进一步途径。
The influence of excessive running load on the development of knee osteoarthritis (OA) was investigated in male Wistar rats. Running exercises were performed in a running wheel using intracranial self-stimulation to motivate Wistar rats to run daily distances of 500 m at 5 days/week. Hereby, ten rats ran a distance of 15 km within three weeks while a further ten rats run a total of 30 km within six weeks. Thirteen Wistar rats without running exercises served as controls. Complete knee joint sections of all rats were evaluated histologically using MANKINs grading system with categorization of the findings into non, mild moderate, and severe osteoarthritis. In addition, immunoreactivity of the chondrocytes to MMP-3 as an important cartilage degrading enzyme in OA was assessed by immunostaining with monoclonal MMP-3 IgG antibodies.Histological assessment of the knee joint sections revealed a significant increase in osteoarthritic changes with higher running load. While in rats with 15 km running all but two knee joints showed mild OA, moderate OA was the predominant finding in rats with 30 km running. In contrast, no OA was found in the controls. Immunostaining for MMP-3 revealed a significant increase in immunoreactivity of the chondrocytes to MMP-3 with higher running load, indicating a running load-depending production of this cartilage-degrading enzyme in the course of increasing OA. Compared to 47.4% immunoreactive chondrocytes to MMP-3 in the controls, this ratio rose to 70.4% in rats with 15 km running and even up to 89.9% in rats with 30 km running.In conclusion, in Wistar rats, excessive running load leads to marked, running distance-depending osteoarthritic changes which are caused, at least in part, by an increase in MMP-3 production rising with greater running distance. Within this exercise model of OA, intracranial self-stimulation is an effective method to motivate Wistar rats to extremely excessive running in a running wheel. This model offers a wide range of further approaches to studying different processes of the development of OA.