Experimental study on the effects of dehydroepiandrosterone on osteoarthritis in rats / 中国临床药理学与治疗学

ABSTRACT

AIM: To investigate the effects of dehydroepiandrosterone (DHEA) on experimental osteoarthritis 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 right knee joints of groups B, C and D. Then the right knee joints of rats in groups C and D, respectively, received 150 ?l intraarticular injections of DHEA at a concentration of 50 ?mol?L~(-1) and 100 ?mol?L~(-1), and the right knee joints of rats in groups A and B both received 150 ?l 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 groups C and D decreased in comparison with group B, and the foregoing indexes in group D decreased significantly compared with group C. However, the activities of superoxide dismutase (SOD) in the douche of articular cavity and blood serum in groups C and D increased in comparison with group B, and the foregoing indexes in group D increased significantly compared with group 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.