Abstract: Objective To explore the intervention effect of down-regulation of HIF-1α on knee osteoarthritis (KOA) model rats and the mechanism of phosphorylation modification of inflammasome ASC pathway and signaling pathway. 
Methods Forty SPF SD rats were randomly divided into control group (n=10), model group (n=10), negative control (NC) group (n=10) and si-HIF-1α group (n=10). The model group, NC group and si-HIF-1α group were used to establish a rat model of KOA. The NC group and the si-HIF-1α group were injected with 5 nmol of NC plasmid and si-HIF-1α plasmid respectively through the tail vein, and the control group and the model group were given the same amount of normal saline.The rat knee joints were analyzed by HE staining and pathological scoring. The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α （TNF-α） in the joint tissues of the rats were detected by enzyme-linked immunosorbent assay (ELISA). The expression levels of HIF-1α and angiotensin I-converting enzyme (ACE) in knee joint tissue of rats, and the protein expression levels of JUN and ASC and the phosphorylation level of signaling pathway in inflammasome of knee joint tissue of rats were detected by Western blot. 
Results Compared with the control group, the knee joint injury and pathological scores in the model group, NC group and si-HIF-1α group were significantly higher than those in the control group, which were lower in the si-HIF-1α group than in the model group and NC group. ELISA results showed that, compared with the control group, IL-1, IL-6, IL-8 and TNF-α in joint tissues of model group, NC group and si-HIF-1α group were significantly increased (P＜0.01), which were significantly lower in the si-HIF-1 group than in the model group and NC group (P＜0.01). qPCR results showed that compared with the control group, JUN and ASC were significantly up-regulated in the model group and NC group, and significantly down-regulated in the si-HIF-1α group (P＜0.01). Western blot results showed that compared with the control group, JUN and ASC in the model group and NC group were significantly increased, while those in the si-HIF-1α group were significantly decreased, and the phosphorylation level of their signaling pathways was significantly decreased (P＜0.01). 
Conclusion Down-regulation of HIF-1α can inhibit the release of inflammatory factors in KOA model rats, reduce tissue damage, and exert bone protective effect. The mechanism may be related to the regulation of phosphorylation modification of the ASC domain of the inflammasome. 

Key words: osteoarthritis, knee, hypoxia-inducible factor 1, inflammasome