连翘苷元通过抑制TLR4介导的NF-κB信号通路减轻大鼠骨关节炎软组织损伤和基质降解

目的研究连翘苷元调控TLR4介导的NF-κB信号通路的活化对骨关节炎大鼠软组织损伤和基质降解的影响。方法建立骨关节炎大鼠模型,将大鼠随机分为6组:健康对照组,模型组,连翘苷元低、中、高剂量组和双醋瑞因组进行后续实验;苏木素-伊红染色和番红O-固绿染色检测大鼠骨关节病理损伤程度;ELISA检测炎症因子的含量;蛋白免疫印迹检测半胱氨酸蛋白酶-3、半胱氨酸蛋白酶-9、聚集蛋白聚糖、基质金属蛋白酶13、Ⅱ型胶原蛋白、Toll样受体4、髓样分化因子88、核因子κB蛋白表达水平。结果与模型组相比较,连翘苷元中、高剂量组和双醋瑞因组骨关节病理损伤程度明显改善,Caspase-3、Caspase-9蛋白水平显著降低(P<0.05),Bcl-2/Bax比值显著升高(P<0.05),Aggrecan、type II collagen(ColⅡ)蛋白水平显著升高(P<0.05),MMP-13蛋白水平显著降低(P<0.05),IL-6、IL-17、TNF-α、MCP-1含量显著降低(P<0.05),TLR-4、MyD88、NF-κB p65蛋白水平显著降低(P<0.05)。结论连翘苷元抑制TLR4介导的NF-κB信号通路的活化对骨关节炎大鼠软组织损伤和基质降解具有修复作用。

Phillygenin repairs the soft tissue injury and matrix degradation by inhibiting TLR4-mediated NF-kappa B signaling pathway in rats with osteoarthritis

The purpose of this study was to investigate the effects of phillygenin on the activation of TLR4-mediated NF-κB signaling pathway,and on soft tissue injury and matrix degradation in osteoarthritis rats.HE staining and safranin O-fast green staining were used to detect the pathological damage of bone and joint in rats;ELISA was used to detected the levels of inflammatory cytokines.Western blot was employed to detected the protein expression levels of Caspase-3,Caspase-9,Bax,Bcl-2,Aggrecan,MMP-13,type II collagen,TLR-4,MyD88 and NF-κB p65.Data showed that phillygenin could down-regulate the pathological damage degree of rats with osteoarthritis,reduce the apoptosis of cartilage tissue,increase the proportion of bone trabecular and cartilage,promote the synthesis of extracellular matrix,and reduce the content of pro-inflammatory cytokines.In conclusion,phillygenin can inhibit the activation of TLR4-mediated NF-κB signaling pathway,and repair soft tissue injury and matrix degradation in osteoarthritis rats.