党参炔苷调节TXNIP/NLRP3信号通路对骨关节炎大鼠软骨损伤的影响

Effect of Lobetyolin on Cartilage Injury in Osteoarthritis Rats by Regulating the TXNIP/NLRP3 Signaling Pathway

目的:探讨党参炔苷调节TXNIP/NLRP3信号通路对骨关节炎(OA)大鼠软骨损伤的影响。方法:将大鼠随机分为Sham组、Model组、党参炔苷低剂量组、党参炔苷高剂量组、党参炔苷高剂量+HY-N2485(NLRP3激活剂)组,每组10只。ELISA检测大鼠血清中TNF-α、IL-1β、IL-4、CTX-Ⅰ、CTX-Ⅱ水平水平;HE和番红O-固绿染色观察关节软骨组织形态学改变;Mankin评分评价软骨退变程度;TUNEL观察大鼠软骨细胞凋亡情况;检测软骨组织NO、MDA和SOD水平;Western blot检测大鼠关节软骨组织MMP-3、MMP-13、Cleaved-caspase-3、TXNIP和NLRP3蛋白表达。结果:与Sham组相比,Model组大鼠软骨组织结构明显破坏,血清IL-1β、TNF-α、CTX-Ⅰ、CTX-Ⅱ水平、Mankin评分、细胞凋亡率、软骨组织中NO、MDA水平、MMP-3、MMP-13、Cleaved-caspase-3、TXNIP、NLRP3蛋白表达水平升高,血清IL-4水平和软骨组织SOD水平降低(P<0.05);与Model组相比,党参炔苷低、高剂量组大鼠软骨组织结构破坏程度减轻,血清IL-1β、TNF-α、CTX-Ⅰ、CTX-Ⅱ水平、Mankin评分、细胞凋亡率、软骨组织中NO、MDA水平、MMP-3、MMP-13、Cleaved-caspase-3、TXNIP、NLRP3蛋白表达水平降低,血清IL-4水平和软骨组织SOD水平升高(P<0.05);HY-N2485可部分逆转党参炔苷对OA大鼠软骨损伤的改善作用(P<0.05)。结论:党参炔苷可降低OA大鼠软骨炎症、氧化应激和细胞凋亡,减轻软骨组织损伤,可能是通过抑制TXNIP/NLRP3信号通路实现的。

Objective:To investigate the effect of Lobetyolin on cartilage injury in osteoarthritis(OA)rats by regulating the TXNIP/NLRP3 signaling pathway.Methods:The rats were randomly divided into sham group,model group,Lobetyolin low-dose group,Lobetyolin high-dose group,and Lobetyolin high-dose+HY-N2485(NLRP3 activator)group,with 10 rats in each group.ELISA was used to measure TNF-α,IL-1β,IL-4,CTX-I,CTX-II levels in rat serum.HE and saffron O-green staining were applied to observe morphological changes in articular cartilage tissue.The Mankin score was used to assess the degree of cartilage degeneration.TUNEL was applied to observe apoptosis of rat chondrocytes.Cartilage tissue NO,MDA,and SOD levels were measured.Western blot was used to detect the protein expression of MMP-3,MMP-13,Cleaved-caspase-3,TXNIP and NLRP3 in rat articular cartilage tissue.Results:Compared with the Sham group,the cartilage tissue structure of the rats in the model group was obviously damaged,the serum IL-1β,TNF-α,CTX-I,CTX-II levels,Mankin score,apoptosis rate,NO and MDA levels in cartilage tissue,MMP-3,MMP-13,Cleaved-caspase-3,TXNIP,NLRP3 protein expression levels increased,the serum IL-4 level and cartilage tissue SOD level decreased(P<0.05).Compared with the model group,the degree of cartilage tissue structure destruction in the Lobetyolin low-dose and high-dose groups was reduced,the serum IL-1β,TNF-α,CTX-I,CTX-II levels,Mankin score,apoptosis rate,NO and MDA levels in cartilage tissue,MMP-3,MMP-13,Cleaved-caspase-3,TXNIP,NLRP3 protein expression levels decreased,the serum IL-4 level and cartilage tissue SOD level increased(P<0.05).HY-N2485 could partially reverse the ameliorating effect of Lobetyolin on cartilage injury in OA rats(P<0.05).Conclusion:Lobetyolin can reduce cartilage inflammation,oxidative stress and apoptosis,and alleviate cartilage tissue damage in OA rats,which may be achieved by inhibiting the TXNIP/NLRP3 signaling pathway.