摘要
目的观察新型蛋白酶体抑制剂(YSY-01A)对兔骨性关节炎(OA)的治疗作用,并探讨其机制。方法将36只健康新西兰大白兔随机分为干预组、模型组、对照组各12只,干预组、模型组均制备OA模型;制模后1周,干预组膝关腔内注射YSY-01A 1 mL,模型组和对照组膝关腔内注射0.9%生理盐水1 mL,每周2次,共8次,共4周。比较各组膝关节软骨病理变化及滑膜组织白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)蛋白阳性细胞数和滑膜组织IκB激酶β(IKKβ)、核因子-κB(NF-κB)、基质金属蛋白酶-9(MMP9)mRNA相对表达量。结果对照组:软骨表面排列平滑、整齐,软骨细胞层次清楚,排列规则;模型组:软骨表面可见缺损,局部裂隙伸入下方,软骨细胞层次不清,细胞呈重度的弥漫性增生;干预组:各层结构相对于模型组好转,分层比价清楚,软骨细胞轻、中度增生,呈现多层次潮线。与对照组比较,干预组和模型组IL-1β、TNF-α蛋白阳性细胞数升高,TGF-β蛋白阳性细胞数降低(P均<0.05);与模型组比较,干预组IL-1β、TNF-α蛋白阳性细胞数降低,TGF-β蛋白阳性细胞数升高(P均<0.05)。与对照组比较,干预组和模型组滑膜组织MMP9、NF-κB、IKKβmRNA相对表达量升高(P均<0.05);与模型组比较,干预组滑膜组织MMP9、NF-κB、IKKβmRNA相对表达量降低(P均<0.05)。结论YSY-01A对兔OA有治疗作用,其机制可能是通过抑制IL-1β、TNF-α表达,增强TGF-β表达,进而阻断IL-1β/IKKβ/NF-κB/MMP9正反馈信号通路。
Objective To observe the therapeutic effect of new type of proteasome inhibitor(YSY-01A)on osteoarthritis(OA)rabbits and to explore its mechanism.Methods Rabbits were randomly divided into three groups:the treatment group,model group,and control group.After the animal models were completed,the rabbits’knee intra-articular cavities in the treatment group were injected with 1 mL YSY-01A.The rabbits in both model group and control group were treated only with 0.9%saline solution 1 mL,for 4 weeks,twice a week,eight times in total.The changes of articular cartilage among these groups were observed.The protein positive cells of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),transforming growth factor-β(TGF-β),and the mRNA expression levels of IKKβ,matrix metalloproteinase-9(MMP-9),nuclear factor-κB(NF-κB)in the synovial tissues of the rabbits in each group were compared.Results In the control group,the surfaces of cartilage were arranged smoothly and orderly,the layers were clear,and the arrangements were regular;in the model group,defects were seen on the surface of cartilage,local fissures extended into the lower part,the layers of chondrocytes were unclear,and the cells showed severe diffuse hyperplasia;in the treatment group,the structures of each layer were improved as compared with those of the model group,and the layers and prices were clear,the chondrocytes were light with medium hyperplasia,and multilevel tide lines.Compared with the control group,the positive cells of IL-1βand TNF-αincreased,while the positive cells of TGF-βdecreased in the treatment group and model group(all P<0.05).Compared with the model group,the positive cells of IL-1βand TNF-αin the intervention group decreased,and the positive cells of TGF-βprotein increased(all P<0.05).Compared with the control group,the relative expression levels of MMP-9,NF-κB and IKKβmRNA in the synovial tissues increased in the treatment group and the model group(all P<0.05).Compared with the model group,the relative expression levels of M
作者
吴培刚
杨学栋
曹振昊
姜厚森
李忠
WU Peigang;YANG Xuedong;CAO Zhenhao;JIANG Housen;LI Zhong(Weifang Medical University,Weifang 261000,China)
出处
《山东医药》
CAS
2020年第12期46-49,共4页
Shandong Medical Journal
基金
山东省医药卫生科技发展计划项目(2016ws0641)。
