第二代蛋白酶体抑制剂对类风湿性关节炎模型大鼠的干预效果及作用机制研究  

Intervention effect and mechanism of second generation proteasome inhibitor on rheumatoid arthritis model rats

作　　者：王平[1] 王华勇[1] 王浩[1] WANG Ping;WANG Huayong;WANG Hao(Department of Rehabilitation,the First People's Hospital of Zaoyang,Zaoyang,Hubei 441200,China)

机构地区：[1]枣阳市第一人民医院康复科,湖北枣阳441200

出　　处：《国际检验医学杂志》2021年第13期1606-1609,共4页International Journal of Laboratory Medicine

摘　　要：目的探究第二代蛋白酶体抑制剂对类风湿性关节炎模型大鼠的干预效果及作用机制。方法选取30只健康SD大鼠,正常组10只SD大鼠不予处理,对剩余20只大鼠进行建模,按照随机数字表法分为模型组和抑制剂组,各10只。在建模成功第1天起每隔2天对抑制剂组SD大鼠腹腔内注射第二代蛋白酶体抑制剂。比较模型组和抑制剂组大鼠建模后不同时间点关节炎评分,采用透射比浊法检测肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-10、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平,采用Western blot法检测核因子-κB(NF-κB)/p65、核因子-κB抑制蛋白α(IκBα)表达情况,采用酶联免疫吸附试验检测IgA、IgM水平。结果与正常组相比,模型组大鼠TNF-α、IL-6、ALT、AST、NF-κB/p65、IgA、IgM水平上升,IL-10、IκBα水平下降,差异有统计学意义(P<0.05);与模型组相比,抑制剂组大鼠TNF-α、IL-6、ALT、AST、NF-κB/p65、IgA、IgM下降,IL-10、IκBα水平上升,差异有统计学意义(P<0.05)。结论使用第二代蛋白酶体抑制剂对类风湿性关节炎模型大鼠进行治疗,能够通过激活IκBα,抑制NF-κB/p65通路,调节大鼠体内的炎症因子,降低关节炎的严重程度,效果显著。Objective To explore the intervention effect and mechanism of the second generation proteasome inhibitor on rheumatoid arthritis model rats.Methods Thirty healthy SD rats were selected,and 10 SD rats in the normal group were not treated,while the remaining 20 rats were modeled and divided into model group and inhibitor group with 10 rats in each group according to random number table method.SD rats in the inhibitor group were intraperitoneally injected with the second generation proteasome inhibitor every 2 days from the first day of successful modeling.Arthritis score of model group and inhibitor group were compared at different time.Tumor necrosis factor-α(TNF-α),interleukin(IL)-6,IL-10,alanine aminotransferase(ALT),aspartate aminotransferase(AST)levels were detected by transmission turbidimetric method.The expressions of nuclear factor-κB(NF-κB)/p65 and IκBαwere detected by Western blot.The levels of IgA and IgM were detected by enzyme-linked immunosorbent assay.Results Compared with the normal group,the levels of TNF-α,IL-6,ALT,AST,NF-κB/p65,IgA and IgM in model group were increased,while the levels of IL-10 and IκBαwere decreased,with statistical significance(P<0.05).Compared with model group,the levels of TNF-α,IL-6,ALT,AST,NF-κB/p65,IgA and IgM in inhibitor group were decreased,while the levels of IL-10 and IκBαwere increased,with statistical significance(P<0.05).Conclusion The treatment of rheumatoid arthritis model rats with second-generation proteasome inhibitors can regulate inflammatory factors in rats and reduce the severity of arthritis by activating IκBαand inhibiting NF-κB/p65 pathway.

关 键 词：第二代蛋白酶体抑制剂 类风湿性关节炎 肿瘤坏死因子 免疫球蛋白 

分 类 号：R593.22[医药卫生—内科学]