摘要
目的：研究脱氢表雄酮(DHEA)对大鼠实验性骨关节炎(OA)的影响。方法：40只大鼠随机分4组：正常对照组、模型对照组、DHEA大、小剂量组。除正常对照组外，其余3组右膝木瓜蛋白酶关节腔注射法建立OA模型。然后DHEA大、小剂量组两组右膝分别关节腔注射50μmmol·L^(-1)和100μmol·L^(-1)的DHEA溶液150μl，正常对照组、模型对照组两组右膝均注入生理盐水150μl，每周2次，注射5周。6周后处死大鼠，大体形态学、组织学、生化及免疫组化的方法评价关节软骨情况。结果：手术显微镜下观察，见DHEA大、小剂量组两组软骨损害均较模型对照组明显减轻。DHEA大、小剂量组Mankin’s评分、关节腔冲洗液一氧化氮含量、滑膜丙二醛含量及关节软骨基质金属蛋白酶-1和9的表达均较模型对照组显著降低，DHEA大剂量组上述指标均较DHEA小剂量组显著降低。且两组关节腔冲洗液和血清超氧化物歧化酶活性均较模型对照组显著升高，DHEA大剂量组上述指标升高均较DHEA小剂量组更明显。结论：DHEA对OA软骨有保护作用，且存在剂量依赖性，保护机制可能是抑制关节软骨基质金属蛋白酶表达、减少一氧化氮释放和增强抗氧化作用。
AIM： To investigate the effects of dehydroepiandrosterne （DHEA） on experimental osteoarthrifts in rats. METHODS： Forty rats were randomly divided into four groups. Group A is normal control group. Osteoarthritic models of rats were established by intraarticular injections of papain into the fight knee joints of groups B, C and D. Then the fight knee joints of rats in groups C and D, respectively, received 150/d intraarticular injections of DHEA at a concentration of 50 μmol·L^-1 and 100μmol·L^-1 , and the right knee joints of rats in gToups A and B both received 150/A physiological saline, twice weekly for five weeks. Six weeks later, all rats were sacrificed, and the articular cartilage was assessed by gross morphologic, histologic, biochemical and immunohistochemical methods. RESULTS： The cartilage damage in groups C and D was much less than that in group B through observation under a surgical microscope. The Mankin＇s score, nitric oxide （NO） in the douche of articular cavity, malondialdehyde （MDA） in synovium, the expression of matrix metalloproteinase-1 and 9 in articular cartilage in gToups C and D decreased in comparison with group B, and the foregoing indexes in gToup D decreased signiticantly compared with group C. However, the activities of superoxide dismutase （SOD） in the douche of articular cavity and blood serum in gToups C and D increased in comparison with group B, and the foregoing indexes in gToup D increased significantly compared with gToup C. CONCLUSIONS： DHEA shows a cartilage-protecting effect which is in a dosage-dependent manner. The mechanism probably is to inhibit the expression of matrix metalloproteinases and to decrease the release of （NO and enhance the antioxidation.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2005年第10期1181-1185,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
关键词
脱氢表雄酮
骨关节炎
基质金属蛋白酶
超氧化物歧化酶
丙二醛
一氧化氮
dehydroepiandrosterone
osteoarthritis
matrix metalloproteinases superoxide dismutase
malondi aldehyde
nitric oxide
