广州中医药大学学报2026，Vol.43Issue(2)：463-471,9.DOI:10.13359/j.cnki.gzxbtcm.2026.02.026
杨梅黄酮靶向 iNOS/NO 以及干预大鼠膝骨关节炎的药效作用机制
Therapeutic Effects of Myricetin Targeting iNOS/NO in a Rat Model of Knee Osteoarthritis
摘要
Abstract
Objective To investigate the therapeutic effects and underlying mechanism of myricetin on knee osteoarthritis(KOA)in a rat model.Methods Sixty healthy male Lewis rats were randomly assigned to five groups:sham-operated group,model group,and low-,medium-,and high-dose myricetin treatment groups.Except for the sham-operated group,KOA was induced in all other groups via medial meniscal transection(MMT).After successful modeling,the respective interventions were administered.During the treatment period,rat body mass was measured weekly,and pain status was assessed using the paw balance test.Upon completion of the treatment,joint cartilage morphology was evaluated by hematoxylin-eosin(HE)staining,Safranin O-Fast Green staining,and Toluidine Blue staining,and scored according to the Osteoarthritis Research Society International(OARSI)scoring system.Nitric oxide(NO)levels in the joint cavity fluid were measured using the nitrate reductase method.Levels of inflammatory factors,including inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6),and interleukin-10(IL-10),in the joint cavity fluid were quantified by enzyme-linked immunosorbent assay(ELISA).The mRNA expression levels of anabolic factors[aggrecan(ACAN),collagen type II alpha 1 chain(Col2a1),SRY-box transcription factor 9(SOX9)]and catabolic factors[a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5),matrix metalloproteinase 3(MMP3),matrix metalloproteinase 13(MMP13)]in cartilage were detected by quantitative real-time polymerase chain reaction(qPCR).iNOS protein expression and activation levels in cartilage were determined by Western Blot.Results Compared with the sham-operated group,the model group exhibited significant pathological damage in the knee joint,a markedly increased OARSI score,and a decreased paw balance ratio.High levels of activated iNOS protein and NO accumulation were detected in the articular cartilage tissue,along with upregulated mRNA expression of catabolic factors(ADAMTS5,MMP3,MMP13).Levels of the inflammatory factors TNF-α,IL-1β,and IL-6 in the joint cavity fluid were significantly elevated,whereas mRNA expression levels of anabolic factors(ACAN,Col2a1,SOX9)and IL-10 level in the joint cavity fluid were decreased;all these differences were statistically significant(P＜0.05).No significant difference in body mass was observed between groups(P＞0.05).Compared with the model group,local pathological damage in the knee joint was ameliorated in all myricetin treatment groups.Specifically,the medium-and high-dose myricetin groups showed significantly reduced OARSI scores(P＜0.05)and increased paw balance ratios(P＜0.05).Furthermore,compared with the model group,the medium-and high-dose myricetin groups demonstrated significantly suppressed iNOS/NO expression and activation,decreased levels of the pro-inflammatory cytokines TNF-α,IL-1β,and IL-6,elevated level of the anti-inflammatory cytokine IL-10,enhanced expression of cartilage anabolic factors(ACAN,Col2a1,SOX9),and reduced expression of catabolic factors(ADAMTS5,MMP3,MMP13);all differences were statistically significant(P＜0.05).No significant changes in body mass were observed(P＞0.05),and the rats exhibited good tolerance to myricetin.Conclusion Myricetin alleviates cartilage pathological damage in rat osteoarthritis by inhibiting the expression and activation of iNOS in the joint cavity fluid and articular cartilage tissue,thereby reducing NO production and accumulation,decreasing the release of inflammatory factors,mitigating pain responses,promoting cartilage anabolism while suppressing catabolism,and ultimately maintaining cartilage homeostasis.关键词
杨梅黄酮/膝骨关节炎/诱导型一氧化氮合酶/一氧化氮/炎症因子/软骨损害/大鼠Key words
myricetin/knee osteoarthritis(KOA)/iNOS/NO/inflammatory factors/cartilage homeostasis/rats分类
医药卫生引用本文复制引用
徐剑峰,王辉,徐泽军,马洁,郑献敏,钟晓琴,王红格,唐超..杨梅黄酮靶向 iNOS/NO 以及干预大鼠膝骨关节炎的药效作用机制[J].广州中医药大学学报,2026,43(2):463-471,9.基金项目
中国博士后科学基金项目(编号:2022M713052) （编号:2022M713052）
国家自然科学基金资助项目(编号:31801207) （编号:31801207）
