壮骨健膝方对兔膝骨关节炎滑膜炎症肝X受体/核因子κB通路的影响

Effects of Zhuanggu Jianxi Decoction on LXRS/NF-κB Pathway in Synovitis of Rabbit Knee Osteoarthritis

目的:基于肝X受体/核因子κB信号通路观察壮骨健膝方对兔膝骨关节炎滑膜炎症模型的影响,探讨其对滑膜炎症的作用及机制。方法:将24只新西兰大白兔随机分为正常组6只和造模组18只。造模组行膝关节腔内注射木瓜蛋白酶建立兔膝骨关节炎滑膜炎症模型。造模成功后将模型兔随机分为模型组、扶他林组和壮骨健膝方组,每组6只。扶他林组和壮骨健膝方组分别给予扶他林混悬液、壮骨健膝方药液灌胃,模型组和正常组给予等量生理盐水灌胃。观察干预前后各组兔膝关节皮温、周径、Lequesne MG评分;膝关节液中IL-1β、TNF-α、基质金属蛋白酶-3(MMP-3)、MMP-13含量;滑膜组织评分;滑膜组织中LXRα、N-CoR、P50、P65 mRNA的表达情况。结果:与正常组比较,模型组兔一般情况差,膝关节皮温、周径、Lequesne MG评分、膝关节液中IL-1β、TNF-α、MMP-3、MMP-13含量、滑膜组织评分、P50和P65 mRNA表达均升高(均P<0.05),滑膜组织中LXRα和N-CoR mRNA表达降低(均P<0.05)。与模型组比较,壮骨健膝方组及扶他林组膝关节皮温、周径、Lequesne MG评分、膝关节液中IL-1β、TNF-α、MMP-3、MMP-13含量、滑膜组织评分、P50和P65 mRNA表达均较低(均P<0.05),壮骨健膝方组LXRα与N-CoR mRNA表达升高(均P<0.05),扶他林组LXRα与N-CoR mRNA表达差异无统计学意义(均P>0.05)。与扶他林组比较,壮骨健膝方组LXRα、N-CoR mRNA表达升高(均P<0.05),关节周径较小(P<0.05),其余指标差异无统计学意义(P>0.05)。结论:壮骨健膝方可能通过调控肝X受体/核因子κB信号通路的转导,减少下游炎症介质分泌,达到抑制膝骨关节炎滑膜炎症反应的作用。

Objective:Based on liver X receptors/nuclear factor-kappa B signaling pathway,the effects of Zhuanggu Jianxi Formula on the synovitis model of rabbit knee osteoarthritis were observed,and the effects and mechanism of Zhuanggu Jianxi Formula on synovitis were discussed.Methods:A total of 24 New Zealand white rabbits were randomly divided into a normal group(n=6)and a model group(n=18).The synovitis model of knee osteoarthritis in rabbits was established by intraarticular injection of papain.After successful modeling,the model rabbits were randomly divided into a model group,a voltaren group and a Zhuanggu Jianxi Formula group,with 6 rabbits in each group.Voltaren group and Zhuanggu Jianxi Formula group were given voltaren suspension and Zhuanggu Jianxi Formula by gavage,and the model group and normal group were given the same amount of normal saline by gavage.The skin temperature,circumference and Lequesne MG scores of the knee joint and the contents of IL-1β,TNF-α,MMP-3,MMP-13 in knee fluid and the synovial tissue score,the expressions of LXRα,N-COR,P50,p65 mRNA in synovial tissue were observed before and after intervention.Results:Compared with the normal group,the rabbits in the model group had a worse general condition,the skin temperature,circumference,Lequesne MG scores of the knee joint,the contents of IL-1β,TNF-α,MMP-3,MMP-13 in knee fluid,synovial tissue score,expressions of P50 and P65 mRNA were significantly increased in model group(P s<0.05),while the expressions of LXRαand N-CoR mRNA in synovial tissue were decreased(P s<0.05).Compared with the model group,the knee joint skin temperature,circumference,Lequesne MG score,the content of IL-1β,TNF-α,MMP-3,MMP-13 in the knee joint fluid,synovial tissue in the Zhuanggu Jianxi Formula group and the voltaren group score,P50 and P65 mRNA expression were all low(P s<0.05).LXRαand N-CoR mRNA expression in Zhuanggu Jianxi Formula group were increased(P s<0.05),and there was no statistical difference in LXRαand N-CoR mRNA expression in voltaren group(P s>0.05).Compared with the voltarin group,the Zhuanggu Jianxi Formula group increased the expression of LXRαand N-CoR mRNA(P s<0.05),and the joint circumference was smaller(P<0.05).There was no statistically significant difference in other indicators(P s>0.05).Conclusion:Zhuanggu Jianxi Formula may inhibit the synovitis response of knee osteoarthritis by regulating the transmission of liver X receptors/nuclear factor-kappa B pathway and reducing the secretion of downstream inflammatory cytokines.