摘要
目的:探讨高良姜素(GAL)对膝骨关节炎(KOA)大鼠软骨损伤及相互作用蛋白1(RIP1)/相互作用蛋白3(RIP3)/混合系激酶区域样蛋白(MLKL)信号通路的影响。方法:建立膝骨关节炎大鼠模型,将大鼠分为对照组、模型组、高良姜素低剂量组、高良姜素高剂量组、Nec-1组、塞来昔布组;测量膝关节肿胀程度,苏木精-伊红(HE)染色观察膝骨关节软骨病理损伤情况,ELISA试剂盒检测炎症因子水平(肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-17(IL-17)),免疫组化检测软骨损伤相关蛋白基质金属蛋白酶-13(MMP-13)及Ⅱ型胶原(CollagenⅡ),免疫印迹法检测RIP1、p-RIP1、RIP3、p-RIP3、MLKL、p-MLKL蛋白表达情况。结果:与对照组相比,模型组膝关节软骨组织结构损伤严重,膝关节肿胀程度严重,Mankin's评分及TNF-α、IL-1β、IL-17、MMP-13、p-RIP1/RIP1、p-RIP3/RIP3、p-MLKL/MLKL表达水平升高,CollagenⅡ表达降低(P<0.05);与模型组相比,高良姜素低剂量组、高良姜素高剂量组、Nec-1组、塞来昔布组膝关节软骨组织损伤减轻,膝关节肿胀程度减轻,Mankin's评分及TNF-α、IL-1β、IL-17、MMP-13、p-RIP1/RIP1、p-RIP3/RIP3、p-MLKL/MLKL表达水平降低,CollagenⅡ表达升高(P<0.05);高良姜素高剂量组、Nec-1组、塞来昔布组各指标比较差异无统计学意义(P>0.05)。结论:高良姜素可通过抑制RIP1/RIP3/MLKL信号通路,减轻炎症反应,改善膝骨关节炎软骨损伤。
Objective:To investigate the efficacy of galangin(GAL)on cartilage damage and receptor-interacting protein 1(RIP1)/receptor-interacting protein 3(RIP3)/mixed-lineage kinase domain-like protein(MLKL)signaling pathway in knee osteoarthritis(KOA)rats.Methods:A rat model of KOA was established,and the rats were separated into control group,model group(KOA group),low and high dose galangin groups(GAL-L,GAL-H groups),Nec-1 group,and celecoxib group(Cel group).The degree of knee joint swelling was measured.Hematoxylin-eosin(HE)staining was applied to observe the pathological damage of knee joint cartilage.ELISA kits were applied to detect levels of inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-17(IL-17).Immunohistochemistry was applied to detect matrix metalloproteinase-13(MMP-13)and collagen Ⅱ.Immunoblotting was applied to detect the expression of RIP1,p-RIP1,RIP3,p-RIP3,MLKL,and p-MLKL proteins.Results:The knee joint cartilage tissue structure of the KOA group was severely damaged,the degree of knee joint swelling was severe,the Mankin's score and expression levels of TNF-α,IL-1β,IL-17,MMP-13,p-RIP1/RIP1,p-RIP3/RIP3,and p-MLKL/MLKL increased,the expression of Collagen Ⅱ decreased compared with the control group(P<0.05).The knee joint cartilage tissue damage in the GAL-L,GAL-H,Nec-1,and Cel groups was reduced,the degree of knee joint swelling decreased,the Mankin's score and expression levels of TNF-α,IL-1β,IL-17,MMP-13,p-RIP1/RIP1,p-RIP3/RIP3,and p-MLKL/MLKL decreased,the expression of Collagen Ⅱ increased compared with the KOA group(P<0.05).The various indicators were not statistically significantly different among the GAL-H group,Nec-1 group,and Cel group(P>0.05).Conclusion:Galangin can alleviate inflammation and improve cartilage damage in KOA by inhibiting the RIP1/RIP3/MLKL signaling pathway.
作者
李旭峰
冷冬月
施斌
LI Xufeng;LENG Dongyue;SHI Bin(Shiyan People's Hospital,Shiyan 442000,Hubei China;Taihe Hospital,Shiyan 442000,Hubei China)
出处
《中国中医骨伤科杂志》
CAS
2024年第6期7-12,共6页
Chinese Journal of Traditional Medical Traumatology & Orthopedics
关键词
高良姜素
信号通路
膝骨关节炎
软骨损伤
galangin
protein signaling pathway
knee osteoarthritis
cartilage damage
