| 彭 侃,鲁 超,胡守业,李 政,武文韬.柚皮苷对骨关节炎软骨破坏的保护作用研究[J].,2020,(13):2418-2424 |
| 柚皮苷对骨关节炎软骨破坏的保护作用研究 |
| Protective Effect of Naringin on Cartilage Destruction in Osteoarthritis |
| 投稿时间：2020-02-07 修订日期：2020-03-04 |
| DOI：10.13241/j.cnki.pmb.2020.13.004 |
| 中文关键词: 柚皮苷 骨关节炎 软骨 NF-κB信号通路 NLRP3信号通路 |
| 英文关键词: Naringin Osteoarthritis Cartilage NF-κB signaling pathway NLRP3 signaling pathway |
| 基金项目:国家自然科学基金面上项目（81772410）；陕西省重点研发计划项目（2019SF-201） |
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| 中文摘要: |
| 摘要 目的：考察柚皮苷对骨关节炎软骨破坏的保护作用。方法：将60只7周龄雄性SD大鼠随机分为假手术组、模型组和柚皮苷组，每组20只。模型组和柚皮苷组大鼠通过切断右膝关节的前交叉韧带建立骨关节炎模型，建模后，柚皮苷组大鼠每天灌胃200 mg / kg的柚皮苷溶液，共灌胃4周。通过番红O/固绿染色和OARSI评分评估大鼠的关节软骨损伤程度。通过免疫组织化学染色检测软骨组织中p-IκBα和NLRP3的表达。通过用IL-1β体外诱导SW1353细胞来模拟骨关节炎软骨细胞的病理微环境，并分别应用NF-κB抑制剂(PDTC)或NLRP3抑制剂(CY-09)处理SW1353细胞。通过RT-PCR和Western blot检测细胞中NF-κB、NLRP3、caspase-1、IL-6、IL-10、IL-18、MMP13和ADAMTS-5的表达。通过Annexin V-FITC/PI法检测细胞凋亡。结果：与模型组相比，柚皮苷组的OARSI评分显著降低（2.63 vs 0.94, P<0.05）。柚皮苷组的p-IκBα和NLRP3蛋白表达水平显著低于模型组（P<0.05）。与IL-1β组相比，IL-1β+柚皮苷组的SW1353细胞中NF-κB、NLRP3、caspase-1、IL-6、IL-18、MMP13和ADAMTS-5的表达水平均显著降低，而IL-10显著升高（P<0.05）。PDTC和CY-09对NF-κB和NLRP3信号通路相关分子的调控作用与柚皮苷一致。与IL-1β组相比，IL-1β+柚皮苷组、IL-1β+PDTC组和IL-1β+CY-09组的细胞凋亡率均显著降低（P<0.05）。结论：柚皮苷可在体内和体外抑制骨关节炎的进展，柚皮苷对骨关节炎的治疗作用部分依赖于对NF-κB和NLRP3信号通路的抑制。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the protective effect of naringin on cartilage destruction in osteoarthritis. Methods: Sixty 7-week-old male SD rats were randomly divided into a sham group, a model group and a naringin group, with 20 rats in each group. The osteoarthritis model was established in the model group and naringin group by cutting the anterior cruciate ligament of the right knee. After modeling, rats in naringin group were given 200 mg/kg naringin solution daily for 4 weeks. The degree of articular cartilage damage in rats was assessed by saffron O/fast green staining and OARSI score. The expression of p-IκBα and NLRP3 in cartilage tissue was detected by immunohistochemical staining. The pathological microenvironment of osteoarthritis chondrocytes was simulated by inducing SW1353 cells with IL-1β in vitro, and SW1353 cells were treated with NF-κB inhibitor (PDTC) or NLRP3 inhibitor (CY-09), respectively. The expressions of NF-κB, NLRP3, caspase-1, IL-6, IL-10, IL-18, MMP13 and ADAMTS-5 were detected by RT-PCR and Western blot. Apoptosis was detected by Annexin V-FITC/PI method. Results: Compared with the model group, the OARSI score of the naringin group was significantly reduced (2.63 vs 0.94, P<0.05). The expression levels of p-IκBα and NLRP3 proteins in the naringin group were significantly lower than those in the model group (P<0.05). Compared with IL-1β group, the expression levels of NF-κB, NLRP3, caspase-1, IL-6, IL-18, MMP13 and ADAMTS-5 in SW1353 cells of IL-1β+naringin group were significantly reduced, while IL-10 significantly increased (P<0.05). PDTC and CY-09 have the same regulatory effect on NF-κB and NLRP3 signaling pathway related molecules as naringin. Compared with the IL-1β group, the apoptosis rates in the IL-1β+naringin group, the IL-1β+PDTC group, and the IL-1β+CY-09 group were significantly reduced (P<0.05). Conclusion: Naringin can inhibit the progression of osteoarthritis in vitro and in vivo. The therapeutic effect of naringin on osteoarthritis depends in part on the inhibition of NF-κB and NLRP3 signaling pathways. |
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