Abstract: Objective To explore whether salvianolic acid B affects cartilage tissue damage, hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) in osteoarthritis rats. Methods A rat model of osteoarthritis was constructed, and rats were randomly divided into sham operation group, osteoarthritis group(anterior cruciate ligment transection, ACLT), nimesulide group, salvianolic acid B high (40 mg/kg), and low (10 mg/kg) dose salvianolic acid B group, and salvianolic acid B+HIF-1 activation group, with 12 rats in each group. The bone structure at the joints of the rats in each group was measured and analyzed by micro-CT machine; The histopathological changes of cartilage were observed by safranin fast green staining and Masson staining; The contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and the activity of inducible nitric oxide syn- thase (iNOS) in rats were measured; The expression levels of HIF-1, VEGF, matrix metalloproteinase 13 (MMP-13) and activated caspase-3 (cleaved caspase-3) in rat cartilage tissue were measured by Western blot. Results Compared with the sham operation group, the cartilage tissue damage of the rats in the osteoarthritis group was severe, and the bone volume fraction (BV/TV) of the ankle bone was decreased, the ratio of ankle bone surface area to bone volume (BSA/BV), serum IL-6, TNF-α contents, iNOS activity, cartilage HIF-1, VEGF, MMP-13, and cleaved caspase-3 protein expression were increased (P<0.05); Compared with the osteoarthritis group, the cartilage tissue of the nimesulide group, the salvianolic acid B high and low dose salvianolic acid B group gradually recovered, and the ankle BV/TV was increased, BSA/BV, serum IL-6, TNF-α contents, iNOS activity, cartilage HIF-1, VEGF, MMP-13, and cleaved caspase-3 protein expression were decreased (P<0.05); Compared with the high-dose salvianolic acid B group, the salvianolic acid B+HIF-1 activation group had increased cartilage tissue injury, and ankle BV/TV was lower, BSA/BV, serum IL-6, TNF-α contents, iNOS activity, cartilage HIF-1, VEGF, MMP-13, and cleaved caspase-3 protein expression were increased (P<0.05). Conclusions Salvianolic acid B can inhibit the expression of HIF-1 and VEGF and relieve osteoarthritis by regulating the HIF-1/VEGF pathway.

Key words: anterior cruciate ligment transection, osteoarthritis, salvianolic acid B, hypoxia-inducible factor-1, vascular endothelial growth factor