| 薛 豹,桑伟林,姜亚飞,马金忠.橙皮素抑制NF-κB通路调控软骨细胞炎性退变的实验研究[J].,2019,19(4):608-613 |
| 橙皮素抑制NF-κB通路调控软骨细胞炎性退变的实验研究 |
| Hesperidin Suppress Inflammatory Degeneration of Chondrocyte by Inhibiting NF-κB Signalling Pathway |
| 投稿时间：2018-05-28 修订日期：2018-06-23 |
| DOI：10.13241/j.cnki.pmb.2019.04.002 |
| 中文关键词: 橙皮素 软骨细胞 骨性关节炎 脂多糖 |
| 英文关键词: Hesperitin Chondrocyte Osteoarthritis Lipopolysaccharide |
| 基金项目:上海市科委基金资助项目（13411950503） |
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| 中文摘要: |
| 摘要 目的：炎症因子所介导的慢性炎症瀑布反应是引起关节软骨退变的的主要原因。橙皮素具有抗炎、抗氧化应激等作用，研究橙皮素对关节软骨细胞炎症因子表达及相关信号通路的影响可以加深对关节软骨退变的认识，进而为其预防、治疗提供新的参考依据。研究橙皮素对人关节软骨细胞退变的影响,并从炎症角度来探讨其具体的分子机制。方法：体外分离培养人关节软骨细胞，首先采用CCK-8方法检测橙皮素对人关节软骨细胞增殖的抑制作用；运用RT-PCR和western blot研究橙皮素对于脂多糖（LPS）诱发的关节软骨细胞炎症反应和分解代谢的影响，运用Western blot研究橙皮素对于LPS所诱导的NF-κB信号通路的激活的影响。结果：当橙皮素的浓度低于10 μM时，对于人关节软骨细胞的生长没有明显的抑制作用；real-time PCR和western blot结果显示，在LPS刺激下，关节软骨细胞中IL-6, TNF-α, MMP9, MMP13的基因表达水平明显升高，而橙皮素可以明显抑制炎症反应的激活；Western blot结果显示在LPS的刺激下，NF-κB信号通路显著激活，IKBα降解，随后P65磷酸化。而在橙皮素预处理组中，IKBα降解减少，P65磷酸化减少，NF-κB信号通路的激活受到了明显的抑制。以上结果均有统计学差异(P<0.05)。结论：橙皮素可通过NF-κB信号通路影响人关节软骨细胞炎症反应和分解代谢相关基因的表达,进而降低关节软骨细胞内外的慢性炎症反应，进而延缓老年性关节软骨退变。 |
| 英文摘要: |
| ABSTRACT Objective: Chronic inflammatory cascade reaction mediated by inflammatory factors is the main cause of chronic de- generation of articular cartilage. Hesperetin has anti-inflammatory, anti oxidative stress effects, to study the effects of hesperetin on the inflammatory reactions and related signaling pathways of chondrocytes can deepen our understanding on the degeneration of the articular cartilage, and its prevention and treatment to provide new reference. To study the effect of hesperidin on degeneration of human chondro- cytes and explore its specific molecular mechanism in terms of inflammation. Methods: We first detection of inhibitory effect of hes- peretin on chondrocytes proliferation by CCK-8 assay; We study the effects of hesperetin on the inflammation and metabolism induced by lipopolysaccharide(LPS) in chondrocytes using RT-PCR and western blot. And we detected the activation of NF-κB signal pathway induced by LPS using western blot. Results: Hesperidin inhibited cell viability in a dose-dependent manner, and up to 10 μM, this com- pound had no significant cytotoxic effects on the human chondrocytes. Real-time PCR showed that LPS increased the expression of IL-6, TNF-α, MMP9 and MMP13 genes at the transcriptional level, while pre-treatment with hesperidin reversed this process in a concentra- tion-dependent manner; Western blot further support the results of RT-PCR. Western blot results showed that NF-κB signaling pathway was activated in the stimulation of LPS, IKB alpha degradation, and then phosphorylation of P65, while pretreatment with hesperetin abolished this effects. The above results were statistically significant(P<0.05). Conclusion: Hesperitin can inhibit the expression of in- flammatory and catabolism genes, and then reduce the chronic inflammation of chondrocytes, thus delaying the degeneration of articular cartilage. |
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