RESUMO
OBJECTIVE:To study the time-effect and dose-effect of paeonol on the apoptosis of knee osteoarthritis(OA)artic-ular chondrocyte in rabbits and the mRNA expression of its related protein Bcl-2 and Bax. METHODS:60 big-ear rabbits were ran-domly divided into normal (normal saline) group,model (normal saline) group,paeonol high-dose,medium-dose and low-dose groups and triamcinolone acetonide(positive drug)group,with 10 rabbits in each group. Except for normal group,OA model was induced by right knee anterior cruciate ligament (ACLT) and the medial meniscus 1/3 resection in those groups. After modeling, different doses of paeonol(0.8,0.4,0.2 mg/kg),triamcinolone acetonide 0.2 mg/kg were injected into right articular cavity twice a week. 4 weeks and 8 weeks after administration,articular cartilage specimens were collected. Ultrapathological structure changes of articular chondrocytes were observed by electron microscope. Apoptosis of cartilage cell was observed by TUNEL and apoptotic index was calculated. mRNA expression of apoptosis related genes of Bcl-2 and Bax in articular cartilage tissue of rabbits were de-tected by in situ hybridization technique. RESULTS:Compared with normal group,articular chondrocyte of model group showed early and middle stage apoptosis morphology change after 4 and 8 weeks,and apoptosis index increased significantly and the mRNA expression of Bcl-2 and Bax was up-regulated (P<0.01);4 and 8 weeks later after administration,compared with model group,apoptosis index decreased and mRNA expression of Bax was down-regulated in paeonol groups,while mRNA expression of Bcl-2 was up-regulated(P<0.05 or P<0.01). Electron microscopy ultrastructural observation showed articular chondrocyte of pae-onol high-dose and middle-dose groups were in early stage of apoptosis.CONCLUSIONS:Paeonol can slow down articular chondro-cyte degeneration and destroy in OA model rabbits in time and dose dependently. Its mechanism may be associated with expression up-regulation of Bcl-2 and expression down-regulation of Bax.