CAJ | 학술논문

目的观察蛋白酶体抑制剂MG-132对骨关节炎软骨及滑膜组织NF-κB信号通路的影响.方法 SD大鼠144只,离断前十字韧带及内侧半月板建立膝关节骨关节炎模型,随机分为四组:MG-132组,造模术后24h于膝关节腔内注射100 μl质量浓度为0.007 g/L的MG-132溶液；DMSO(二甲基亚砜,Dimethyl sulfoxide)组,造模术后24h于膝关节腔内注射100μl体积分数为0.1％的DMSO溶液；假手术组,仅行关节囊切开；正常对照组,仅于膝关节腔内注射100μl质量浓度为0.007 g/L的MG-132溶液.术后2、4和12周处死动物,于膝关节软骨组织及滑膜组织取材,行病理形态学观察,根据Mankin评分标准进行半定量评估；应用RT-PCR法检测NF-κB p65、I-κB、TNF-α、IL-1β等基因mRNA的表达水平；荧光分光光度法检测20S蛋白酶体活性,并行相关性分析.结果 MG-132组各时相的Mankin评分均比DMSO组低,假手术组与正常对照组相近且较前两组低,差异有统计学意义.MG-132组各时相的软骨及滑膜组织中NF-κB p65、IL-1β、TNF-α mRNA表达水平均低于DMSO组,除2周滑膜组织NF-κB p65和12周软骨组织IL-1β mRNA外差异均有统计学意义.MG-132组术后2周软骨组织及4周滑膜组织I-κB mRNA表达水平高于DMSO组,差异有统计学意义.结论 MG-132具有减轻滑膜炎症、保护关节软骨的作用,从而延缓骨关节炎进程.
목적 관찰단백매체억제제MG-132대골관절염연골급활막조직NF-κB신호통로적영향.방법 SD대서144지,리단전십자인대급내측반월판건립슬관절골관절염모형,수궤분위사조:MG-132조,조모술후24h우슬관절강내주사100 μl질량농도위0.007 g/L적MG-132용액；DMSO(이갑기아풍,Dimethyl sulfoxide)조,조모술후24h우슬관절강내주사100μl체적분수위0.1％적DMSO용액；가수술조,부행관절낭절개；정상대조조,부우슬관절강내주사100μl질량농도위0.007 g/L적MG-132용액.술후2、4화12주처사동물,우슬관절연골조직급활막조직취재,행병리형태학관찰,근거Mankin평분표준진행반정량평고；응용RT-PCR법검측NF-κB p65、I-κB、TNF-α、IL-1β등기인mRNA적표체수평；형광분광광도법검측20S단백매체활성,병행상관성분석.결과 MG-132조각시상적Mankin평분균비DMSO조저,가수술조여정상대조조상근차교전량조저,차이유통계학의의.MG-132조각시상적연골급활막조직중NF-κB p65、IL-1β、TNF-α mRNA표체수평균저우DMSO조,제2주활막조직NF-κB p65화12주연골조직IL-1β mRNA외차이균유통계학의의.MG-132조술후2주연골조직급4주활막조직I-κB mRNA표체수평고우DMSO조,차이유통계학의의.결론 MG-132구유감경활막염증、보호관절연골적작용,종이연완골관절염진정.
Objective To observe the effect of MG-132 on NF-κB signal path of cartilage and synovium in a rat model of knee osteoarthritis.Methods The rat models of knee osteoarthritis were established by performing anterior cruciate ligament amputation and partial medial meniscectomy.Totally 144 adult SD rats were randomly divided into 4 groups:MG-132 group,100 ml 0.007 g/L MG-132 solution was injected in to the knee joints of rat model 24 h after surgery; DMSO group,100 ml 0.1％ DMSO solution was injected 24 h after surgery; sham surgery group,merely the knee capsulotomy was performed and no solution was injected;control group,100 ml 0.007 g/L MG-132 solution was injected into the knee joints.The cartilage and synovium specimens were obtained at 2,4,12 weeks postoperatively.Pathomorphological observation was taken.The levels of NF-κB p65,I-κB,TNF-α and IL-1β at mRNA were detected by real-time PCR,and the activityof 20S proteasome was measured by fluorospectrophotometry.Resnlts The Mankin score of MG-132 groupwas lower than that of DMSO group.The Mankin scores of sham surgery and control groups were lower thanthose of MG-132 and DMSO groups with significant difference.The mRNA levels of NF-κB p65,IL-1 β,TNF-α of cartilage and synovium in MG-132 group were lower than those of DMSO group with significant differenceexcept for NF-κB p65 of synovium at 2 weeks and IL-1β of cartilage at 12 weeks.The mRNA levels of I-κB of cartilage at 2 weeks and I-κB of synovium at 4 weeks in MG-132 group were higher than those in DMSO group with statistical significance.Conclusion MG-132,the proteasome inhibitor,could postpone the progress of osteoarthritis through alleviating synovial inflammation and defending the articular cartilage.