Objective To analyze the mechanism of tradition Chinese medicine for tonifying kidney, activating blood circulation and removing dampness in the treatment of knee osteoarthritis (KOA) based on nuclear factor-κB (NF-κB) signal pathway.
Methods KOA model was established by anterior cruciate ligament transection (ACLT) in the rats of model control group, dexamethasone group, and groups with various doses of traditional Chinese medicine for tonifying the kidney, activating blood circulation and removing dampness (low dose of traditional Chinese medicine group and high dose of traditional Chinese medicine group).No operation was given for rats in the normal control group; the dexamethasone group, the low dose of traditional Chinese medicine group and the high dose of traditional Chinese medicine group were given corresponding doses of drugs for gavage (50, 50 and 100 mg/kg)on the first day, and the gavage was lasted for 4 weeks; normal control group and model control group were given equal volume of normal saline.When the experiment was over, the paw withdrawal thermal latency (PWTL) and Mankin′s score of rats were measured.Levels of serum interleukin-4(IL-4), interleukin-1b (IL-1b) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay; the levels of microRNA-26a (miR-26a), NF-κB and toll-like receptor 4(TRL4) in synovial tissues of knee joints were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot.
Results Compared with the normal control group, PWTL in the model control group shortened significantly, while the Mankin′s score, IL-1b, IL-4, TNF-α and mRNA and protein expression levels of miR-26a, NF-κB and TRL4 prolonged significantly (P < 0.05).Compared with the model control group, PWTL prolonged significantly, while the Mankin′s score (except for the low dose of traditional Chinese medicine group), IL-1b, IL-4, TNF-α and mRNA and protein expression levels of miR-26a, NF-κB and TRL4 decreased significantly in the low dose of traditional Chinese medicine group, high dose of traditional Chinese medicine group and dexamethasone group, and PWTL in high dose of traditional Chinese medicine group was significantly longer than that in the low dose of traditional Chinese medicine group, while the Mankin′s score, IL-1b, IL-4, TNF-α and mRNA and protein expression levels of miR-26a, NF-κB and TRL4 were significantly lower than those in low dose of traditional Chinese medicine group (P < 0.05).Compared with dexamethasone group, PWTL shortened significantly, while the Mankin′s score, IL-1b, IL-4, TNF-α and mRNA and protein expression levels of miR-26a, NF-κB and TRL4 increased significantly in low dose of traditional Chinese medicine group (P < 0.05).Compared with dexamethasone group, PWTL shortened slightly while the Mankin′s score, IL-1b, IL-4, TNF-α and mRNA and protein expression levels of miR-26a, NF-κB and TRL4 increased slightly in high dose of traditional Chinese medicine group, and there were no significant differences between two groups (P>0.05).
Conclusion Tradition Chinese medicine for tonifying kidney, activating blood circulation and removing dampness can significantly inhibit the inflammatory response of KOA, and its mechanism may be related to the inhibition on expression levels of miR-26a mRNA, NF-κB mRNA and TRL4 mRNA, and inhibition on activation of miR-26a/NF-κB/TRL4 pathway.
DownLoad: