miR-125b-5p对膝骨关节炎模型大鼠的干预效果及作用机制研究  

Study on the intervention effect and action mechanism of miR-125b-5p on knee osteoarthritis model rats

作　　者：崔树北[1] 颜继英[1] 贾晓川[1] 仝路[1] 李毅 张开 刘振武[1] CUI Shubei;YAN Jiying;JIA Xiaochuan;TONG Lu;LI Yi;ZHANG Kai;LIU Zhenwu(Department of Orthopaedics,Handan Central Hospital,Handan,Hebei 056000,China)

机构地区：[1]邯郸市中心医院骨一科,河北邯郸056000

出　　处：《医学动物防制》2025年第4期391-396,402,共7页Journal of Medical Pest Control

基　　金：河北省医学科学研究课题计划(20220015)。

摘　　要：目的探究microRNA-125b(miR-125b)-5p介导凋亡蛋白酶激活因子-1(apoptotic protease activating factor-1,APAF1)/含半胱氨酸的天冬氨酸蛋白水解酶(cysteinyl aspartate specific proteinase,Caspase)凋亡通路对膝骨关节炎(knee osteoarthritis,KOA)模型大鼠膝关节的保护机制。方法2022年2月—2023年2月将大鼠随机分为假手术组、KOA组、阴性对照(negative control,NC)组和下调miR-125b-5p组,比较不同实验方法各组大鼠关节肿胀度、国际骨关节炎研究协会评分和滑膜炎症评分,检测大鼠滑膜组织miR-125b-5p表达,同时进行病理和凋亡分析,另外检测滑膜组织肿瘤坏死因子α(TNF-α)、核因子κB(nuclear factor kappa-B,NF-κB)水平和Caspase3、Caspase7、Caspase9及APAF1蛋白表达。组间比较采用t检验。结果与假手术组相比,KOA组和NC组大鼠关节肿胀度、国际骨关节炎研究协会评分、滑膜炎症评分、miR-125b-5p、TNF-α、NF-κB、滑膜细胞凋亡比例、Caspase3、Caspase7、Caspase9及APAF1蛋白表达水平均显著升高(t=24.696、18.199、36.744、10.525、19.692、76.411、14.141、6.073、10.633、5.750、3.210、23.941、19.240、30.323、8.217、19.782、66.054、13.916、6.139、7.319、7.340、2.412,均P<0.05);与KOA组相比,下调miR-125b-5p组大鼠的关节肿胀度[(2.875±0.327)mm]、国际骨关节炎研究协会评分[(9.25±1.57)分]和滑膜炎症评分[(1.62±0.05)分]显著降低,两组结果差异有统计学意义(t=-6.124、-9.660、-24.063,P<0.05)。结论下调miR-125b-5p对膝骨关节炎模型大鼠滑膜具有保护作用,可以抑制炎症因子释放和滑膜组织细胞凋亡,其机制可能与凋亡信号通路APAF1/Caspase的调控相关。Objective To investigate the protective mechanism of microRNA-125b(miR-125b)-5p-mediated apoptotic protease activating factor-1(APAF1)/cysteinyl aspartate specific proteinase(Caspase)pathway on the knee joint of rats with knee osteoarthritis(KOA)model.Methods From February 2022 to February 2023,rats were randomly divided into sham group,KOA group,negative control(NC)group,and downregulated miR-125b-5p group.Comparison of joint swelling degree and osteoarthritis research society international scores and synovial membrane inflammation scores in groups of rats with different experimental methods.Detection of miR-125b-5p expression in synovial membrane tissues of rats,as well as pathological and apoptotic analyses.The levels of synovial membrane tissue tumor necrosis factorα(TNF-α)and nuclear factor kappa-B(NF-κB)were detected as well as the levels of Caspase3,Caspase7,Caspase9,and apoptosis activating factor(APAF1)protein expression.Comparisons between groups were performed using a t-test.Results Compared to the sham group,joint swelling,osteoarthritis research society international score,synovial membrane inflammation score,miR-125b-5p,TNF-α,NF-κB,synovial membrane cell apoptosis ratio,Caspase3,Caspase7,Caspase9,and APAF1 protein expression were all significantly higher in the KOA and NC groups(t=24.696,18.199,36.744,10.525,19.692,76.411,14.141,6.073,10.633,5.750,3.210,23.941,19.240,30.323,8.217,19.782,66.054,13.916,6.139,7.319,7.340,2.412,all P<0.05).Compared with the KOA group,joint swelling degree[(2.875±0.327)mm],Osteoarthritis Research Society International score[(9.25±1.57)score],and synovial membrane inflammation score[(1.62±0.05)score]were significantly reduced in the downregulated miR-125b-5p group,and the difference between the results of the two groups was statistically significant(t=-6.124,-9.660,-24.063,P<0.05).Conclusion Downregulation of miR-125b-5p has a protective effect on the synovium of knee osteoarthritis model rats,which can inhibit the release of inflammatory factors and the apoptosis

关 键 词：miR-125b-5p 膝骨关节炎 滑膜 炎症 APAF1/Caspase信号通路 

分 类 号：R614[医药卫生—麻醉学]