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Patho-parmacological Studies for Vascular Eendothel in Osteonecrosis of Femoral Head in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP).

易中风自发性高血压大鼠 (SHRSP) 股骨头坏死中血管内皮细胞的病理学研究。

基本信息

批准号：
15591590
负责人：
KUMAGAI Kenji
金额：
$ 2.24万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Studies for human osteonecrosis of the femoral head(ONFH) have shown that a close parallelism between steroid hormone-related hyperlipemia and oxidization stress-induced endothelium dysfunction140 male SHRSP/Ngsk, maintained and bred at our university.At 15 weeks of age, rats were grouped to four at random. The first group was the control group. The second group was the HFC diet group, was fed the HFC diet. The third group was the steroid hormone administrated group, was fed the SP diet, and steroid hormone was injected. The fourth group was the Steroid Hormone plus HFC diet group, was given the HFC diet and treated with a steroid hormone. These rats were decapitated at 19th weeks of age.The regime of the HFC diet is consisted of 68%, SP diet (Funabashi Farm Co ltd),5% Cholesterol,2% Cholic acid,25% Beef tallow powder and 0.006% NG-nitro-L-arginine as a NOS inhibitor.As a steroid hormone,5mg Methyl-predonisolon was injected into the dorsal muscular layer at 17th weeks of age. Hematoxylin-Eosin staining for the check about ONFH, Tunnel's method to examine the apoptosis in the femoral head and immunostaining with anti 8-OHdG(8-hydroxy-deoxyguanosine) and anti 4-HNE(4-hydroxy-2-nonenal) were performed as pathological examinations.The study indicated that steroid hormone was very effective of osteonecrosis.Apoptosis was found not only in the femoral epiphysis but in the shaft around the necrosis, where the much adipocyte degeneration was found. So the adipocyte degeneration was suggested migration to necrosis.More oxidation stress might be existed in the bone marrow of femoral head in the steroid hormone plus HFC diet group, especially at the arteries around femoral head. It suggests that the oxidation stress may trigger the ischemic change.This study contributed the participation of hyperlipemia and oxidization stress related to the cause of femoral head avascular necrosis in humans.

对人类股骨头坏死(ONFH)的研究表明，类固醇激素相关性高脂血症和氧化应激诱导的内皮功能障碍之间存在密切的平行关系。140只雄性SHRSP/NGSK在我校饲养。第一组为对照组。第二组为HFC饮食组，给予HFC饮食。第三组为类固醇激素组，给予SP饲料，注射类固醇激素。第4组为激素+HFC饮食组，给予HFC饮食并给予激素治疗。19周龄处死大鼠，HFC饲料配方为68%、SP饲料(船桥农场有限公司)、5%胆固醇、2%胆酸、25%牛脂粉和0.006%一氧化氮合酶抑制剂NG-硝基-L-精氨酸。17周龄时背肌层注射甲基强的松龙5 mg作为类固醇激素。病理检查采用苏木精-伊红染色，Tunes法检测股骨头细胞凋亡，抗8-OHdG(8-羟基脱氧鸟苷)和抗4-HNE(4-羟基-2-壬烯醛)免疫组织化学染色。研究表明，类固醇激素对骨坏死有很好的治疗作用。细胞凋亡不仅发生在股骨骺，而且发生在坏死周围脂肪细胞变性较多的骨干部位。激素加HFC饮食组大鼠股骨头骨髓中可能存在更多的氧化应激，尤其是股骨头周围动脉。提示氧化应激可能触发了股骨头缺血性改变，高脂血症和氧化应激参与了股骨头缺血坏死的发生。