Osteonecrosis in stroke-prone spontaneously hypertensive rats: effect of glucocorticoid
Osteonecrosis in stroke-prone spontaneously hypertensive rats: effect of glucocorticoid
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DOI：
10.1007/s00776-007-1129-y
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发表时间：
2007-05-01
影响因子：
1.7
通讯作者：
Shindo, Hiroyuki
中科院分区：
文献类型：
--
作者：
Murata, Masakazu;Kumagai, Kenji;Shindo, Hiroyuki
背景 高剂量施用类固醇激素与骨坏死的主要风险相关。在本研究中，我们研究了类固醇激素对易发生中风的自发性高血压大鼠/长崎（SHRSP/Ngsks）股骨头坏死发生率的影响。方法将总共 71 只 SHRSP/Ngsks 分为两组：对照组（C 组，n = 40）和类固醇激素组（S 组，n = 31）给予 5 mg（约 第 17 周龄期间给予醋酸甲泼尼龙 20 mg/kg。我们使用抗4HNE和抗8OHdG单克隆抗体对各组的实验室数据、组织学表现、骨坏死发生率和氧化应激表达进行免疫组化分析。结果S组总胆固醇升高，高密度脂蛋白、低密度脂蛋白和甘油三酯含量均显着高于C组。组织学检查显示，S组股骨头坏死发生率（95.2%）明显高于C组（51.2%）。两组骨坏死的大多数组织学特征都表现出类似的典型特征。然而，S组显示股骨头中的骨髓空间被数量增加的脂肪细胞占据并且肿胀、部分退化和坏死。免疫组织化学分析显示，S组的抗4HNE和抗8OHdG抗体染色强于C组。结论本研究在很大程度上证实了类固醇激素的施用增加了骨髓中脂肪细胞数量的怀疑。还观察到脂肪变性和坏死，被认为是骨坏死的早期征兆。据推测，骨坏死是由骨髓中伴随室压负荷的缺血性变化引起的，其中脂肪变性、坏死和内皮细胞损伤可能与氧化应激一起发生。
Background High-dose administration of a steroid hormone has been associated with a major risk of osteonecrosis. In this study we investigated the effects of a steroid hormone on the incidence of osteonecrosis of the femoral head in stroke-prone spontaneously hypertensive rats/Nagasaki (SHRSP/Ngsks).Methods A total of 71 SHRSP/Ngsks were divided into two groups: a control group (C group, n = 40) and a steroid hormone group (S group, n = 31) given 5 mg (about 20 mg/kg) of methylprednisolone acetate during the 17th week of age. We compared the groups' laboratory data, histological appearance, incidence of osteonecrosis, and expression of oxidative stress on immunohistochemical analysis using the monoclonal antibodies anti-4HNE and anti-8OHdG.Results The S group showed an increase in total cholesterol, with the amounts of high-density lipoprotein, low-density lipoprotein, and triglycerides all significantly higher than in the C group. Histological examination showed that the frequency of necrosis of the femoral head was significantly higher in the S group (95.2%) than in the C group (51.2%). Most of the histological features of the osteonecrosis demonstrated typical features of a similar sort in the two groups. However, the S group showed bone marrow spaces in the femoral head that were occupied by an increased number of adipocytes and that were swollen, partially degenerative, and necrotic. On immunohistochemical analysis, the stains of anti-4HNE and anti-8OHdG antibody were stronger in the S group than in the C group.Conclusions This study confirmed, to a remarkable degree, the suspicion that the administration of steroid hormone increases the number of adipocytes in marrow. Fat degeneration and necrosis, considered early signs of osteonecrosis, were also observed. It has been hypothesized that osteonecrosis is produced by the ischemic change accompanying compartment pressure load in marrow, where fat degeneration, necrosis, and endothelial cell injury might occur together with oxidative stress.