血管活性肠肽和NF-κB信号通路在骨关节炎中的作用机制

Mechanism of Action of Vasoactive Intestinal Peptide and NF-κB Signaling Pathway in Osteoarthritis

为了考察血管活性肠肽和NF-κB信号通路在骨关节炎中的作用机制,本研究以5周龄SD雄性大鼠为研究材料,通过改良Hulth法建立骨关节炎大鼠模型,然后向大鼠关节内注射血管活性肠肽质粒进行治疗。研究显示,骨关节炎大鼠软骨细胞数量明显减少,细胞弥漫性增加,出现大量细胞簇。在用血管活性肠肽质粒处理后,大鼠膝关节的病理改变显著改善,并且OARSI评分显著降低(p<0.05)。血管活性肠肽质粒处理可显著降低大鼠血清IL-2和TNF-α水平,并升高IL-4水平(p<0.05)。血管活性肠肽质粒处理可显著降低滑膜细胞的增殖能力(p<0.05)。血管活性肠肽质粒处理可显著上调滑膜细胞中的CollagenⅡ和Osteoprotegerin蛋白表达,并下调ADAMTS-5和MMP-13蛋白表达。血管活性肠肽质粒处理可显著下调p-p65表达,并上调p-IκBα表达。综上所述,本研究表明血管活性肠肽可通过抑制滑膜细胞增殖、炎症反应、软骨退变等作用来治疗骨关节炎,其作用机制与抑制NF-κB信号通路的激活有关。

To investigate the mechanism of action of vasoactive intestinal peptide and NF-κB signaling pathway in osteoarthritis.In this study,5-week-old SD male rats were used as research materials to establish a rat model of osteoarthritis by modified Hulth method,and then the rats were injected intra-articular injection of vasoactive intestinal peptide plasmid.Studies showed that the number of chondrocytes in osteoarthritis rats was significantly reduced,the cells were diffusely increased,and a large number of cell clusters appeared.After treatment with the vasoactive intestinal peptide plasmid,the pathological changes in the knee joint of rats were significantly improved and the OARSI score was significantly reduced(p<0.05).Vasoactive intestinal peptide plasmid treatment significantly reduced serum IL-2 and TNF-αlevels and increased IL-4 levels(p<0.05).Vasoactive intestinal peptide plasmid treatment significantly reduced the proliferation of synoviocytes(p<0.05).Vasoactive intestinal peptide plasmid treatment significantly up-regulated the expressions of CollagenⅡand Osteoprotegerin and down-regulated the expressions of ADAMTS-5 and MMP-13 in synoviocytes.Vasoactive intestinal peptide plasmid treatment significantly down-regulated p-p65 expression and up-regulated p-IκBαexpression.In summary,this study demonstrates that vasoactive intestinal peptide can treat osteoarthritis by inhibiting synovial cell proliferation,inflammatory response,cartilage degeneration,etc.,and its mechanism is related to inhibition of NF-κB signaling pathway activation.