关键词: 骨关节炎, 鼠曲草提取物, 炎性反应, 氧化应激反应, 白激酶受体 R 样内质网激酶, 真核翻 译起始因子 2a, CCAAT/ 增强子结合蛋白同源蛋白 

Abstract: Objective To explore the effect of gnaphalium affine extract (GAE) on the anterior cruciate ligament transverse (ACLT) -induced osteoarthritis (OA) in rats. Methods A total of 90 SPF-level healthy male SD rats were randomly divided into 6 groups (15 rats in each group): sham group, model group, GAE low-dose group (400 mg / kg), GAE medium-dose group (800 mg / kg), GAE high-dose group (1 600 mg / kg), and diacerein group (54 mg / kg). OA Rat model was established in above groups by performing the ACLT surgery except in the sham group, GAE or diacerein treatment were given to the rats in the corresponding groups for 30 d. The pathological damage of knee cartilage tissues was observed by HE staining. Enzyme-linked immunosorbent assay was used to measure the levels of inflammatory factors in serum and synovial fluid. The levels of oxidative stress factors in synovial fluid were measured by colorimetry. The expression levels of protein kinase R-like endoplasmic reticulum kinase / eukaryotic translation initator factor-2α / C / EBP homologous protein (PERK/ eIF2a / CHOP) signaling pathway related proteins in knee tissues were detected by Western blotting. Results The rat cartilage surfaces in the sham group were smooth and intact. The rat cartilage tissues in the model group and GAE low-dose group were severely damaged, the stratified structures of the articular cartilages were blurred and cell arrangements were disordered. The pathological damages in rats from the GAE medium-and high-dose groups and the diacerein group were significantly relieved compared with those from the model group. The Mankin’s score of rats was higher in the model group. The levels of serum and synovial fluid tumor necrosis factor-α (TNF-α), interleukin-6 ( IL-6 ) and interleukin-1β ( IL-1β) in the model group were higher than those in the sham group (P < 0. 05). The level of synovial fluid malondialdehyde (MDA) in the model group was higher than that in the sham group (P< 0. 05), while the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were lower (P < 0. 05). The expression levels of PERK, eIF2a and CHOP were higher in the model group than in the sham group (P < 0. 05). The Mankin’s score of the rats in the GAE medium-and high-dose groups and the diacerein group was lower. The levels of serum and synovial fluid TNF-α, IL-6 and IL-1β in the GAE medium-and high-dose groups and the diacerein group were lower than those in the model group (P < 0. 05). The synovial fluid MDA level in the GAE medium-and high-dose groups and the diacerein group was lower (P< 0. 05), while the levels of SOD and GSH-Px were higher than those in the model group (P< 0. 05). The expression levels of PERK, eIF2a and CHOP were lower in the GAE medium-and high-dose groups and the diacerein group than in model group (P< 0. 05). Conclusion An appropriate dosage of GAE can significantly improve the pathological damage of knee joints, reduce the inflammatory response and oxidative stress, and inhibit the activity of PERK/ eIF2a / CHOP signaling in the OA rats. 

Key words: osteoarthritis, gnaphalium affine extract, inflammatory response, oxidative stress response, protein kinase R-like endoplasmic reticulum kinase, eukaryotic translation initator factor-2α, C / EBP homologous protein