单纯激素-New insights into the pathogenesis of glucocorticoid-induced avascular necrosis microarray analysis of gene expression in a rat model.pdfVIP

Kerachian et al. Arthritis Research Therapy 2010, 12:R124 /content/12/3/R124 R E S E A R C H A R T I C L E Open Access Research article New insights into the pathogenesis of glucocorticoid-induced avascular necrosis: microarray analysis of gene expression in a rat model 1 1,2,3 4 3 5 6 Mohammad Amin Kerachian , Denis Cournoyer , Edward J Harvey , Terry Y Chow , Louis R Bégin , Ayoub Nahal and Chantal Séguin*2,3 Abstract Introduction: Avascular necrosis of the femoral head (ANFH) occurs variably after exposure to corticosteroids. Microvascular thrombosis is a common pathological finding. Since systemic thrombophilia is only weakly linked with ANFH, we propose that microvascular vessel pathology may be more related to local endothelial dysfunction and femoral head apoptosis. Corticosteroid effects on the endothelium and resultant apoptosis have been reported. We hypothesize that corticosteroids contribute to a differential gene expression in the femoral head in rats with early ANFH. Methods: Besides bone marrow necrosis, which is a common sign in ANFH and reported in the early stages, we include the presence of apoptosis in this study as a criterion for diagnosing early disease. Forty Wistar Kyoto (WKY) rats were randomized to either a corticosteroid-treated group or an age-matched control group for six months. After sacrifice, the femoral heads were examined for ANFH. Total mRNA was extracted from femoral heads. Affymetrix exon array (Santa Clara, CA, USA) was performed on 15 selected RNA samples. Validation methods included RT-PCR and immunohistochemistry (IHC). Results: Although rat exon array demonstrated a significant upregulation of 51 genes (corticosteroid(+)/ANFH(+) VS co