银杏内酯C对2种骨关节炎模型中软骨病理变化、基质降解和炎症反应的影响  

Effects of ginkgolide C on cartilage pathologic changes,matrix degradation,and inflammatory responses in two osteoarthritis models

作　　者：贾丽娜 巩颖超 樊夏楠 蒋欣茹 嵇正华 赵明超 常轶聪 李睿[1,2] 刘芳萍 JIA Lina;GONG Yingchao;FAN Xianan;JIANG Xinru;JI Zhenghua;ZHAO Mingchao;CHANG Yicong;LI Rui;LIU Fangping(College of Veterinary Medicine,Northeast Agricultural University,Harbin 150030,China;Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development,Harbin 150030,China)

机构地区：[1]东北农业大学动物医学学院,黑龙江哈尔滨150030 [2]黑龙江省动物疾病防控技术与制剂创制重点实验室,黑龙江哈尔滨150030

出　　处：《中国兽医学报》2024年第7期1489-1497,共9页Chinese Journal of Veterinary Science

摘　　要：基于大鼠关节疼痛、软骨病理程度、ECM降解过程和炎症介质生成水平,探究银杏内酯C(GC)对2种造模方式的软骨保护效果。选取25只Sprague-Dawley大鼠随机分为5组:对照组(Control组)、模型1组(ACLT组)、给药1组(ACLT+GC组)、模型2组(MIA组)和给药2组(MIA+GC组)。试验4周后,收集大鼠右后肢股骨、胫骨和血液样本,应用番红O固绿染色和OARSI评分对大鼠股骨和胫骨病理程度进行评估;免疫组化检测软骨中CollagenⅡ和MMP-13的表达水平;ELISA检测大鼠血清中MMP-3、MMP-13、CTX-Ⅱ、COMP、COX-2、INOS、IL-1β和TNF-α的水平变化;冷敏感性试验和伸膝发声试验检测大鼠关节疼痛程度。结果显示,与MIA组相比,ACLT可造成更严重关节软骨结构损伤。ACLT组中股骨和胫骨的OARSI评分、MMP-13的表达和血清中MMP-13、MMP-3、CTX-Ⅱ、COMP水平均高于MIA组;然而ACLT组中炎症介质COX-2、IL-1β和TNF-α水平显著低于MIA组(P<0.01)。GC干预后可降低OARSI评分(P<0.05或P<0.01)和疼痛评分,抑制ECM基质降解酶(MMP-13、MMP-3)、软骨代谢标志物(CTX-Ⅱ、COMP)和炎症介质(COX-2、INOS、IL-1β和TNF-α)的表达,并促进CollagenⅡ的合成。结果表明,2种造模方式均可造成软骨损伤,其中ACLT+PMMx法构建OA模型中大鼠关节损伤明显,有利于研究软骨结构损伤程度。GC干预后可减轻2组大鼠OA模型中关节疼痛、软骨病理变化、基质降解程度和炎症反应,从而发挥保护软骨作用。The cartilage-protective effect of ginkgolide C(GC)on the two modeling modalities was investigated based on joint pain,degree of cartilage pathology,ECM degradation process,and level of inflammatory mediator production in rats.Twenty-five SD rats were selected and randomly divided into five groups:the control group(Control group),model 1group(ACLT group),administration 1group(ACLT+GC group),model 2group(MIA group),and administration 2group(MIA+GC group.)The rats were euthanized after 4weeks of the test.Femur,tibia and blood samples were collected from the right hind limb of rats.The degree of pathology in the femur and tibia of rats was assessed by saffron O solid green staining and OARSI score.Immunohistochemistry was used to detect the expression levels of collagenⅡand MMP-13in cartilage.ELISA was used to detect the changes in the levels of MMP-3,MMP-13,CTX-Ⅱ,COMP,COX-2,INOS,IL-1β,and TNF-αin the serum of rats.Cold sensitivity test and knee extension vocalization test were conducted to detect the degree of joint pain in rats.ACLT could cause more severe structural damage to articular cartilage compared with the MIA group.The OARSI scores and the expression of MMP-13in femur and tibia,and the serum levels of MMP-13,MMP-3,CTX-Ⅱ,and COMP were higher in the ACLT group than those in the MIA group.However,the levels of inflammatory mediators COX-2,IL-1β,and TNF-αwere significantly lower in the ACLT group than in the MIA group(P<0.01).GC intervention reduced the OARSI score(P<0.05or P<0.01)and pain scores,inhibited the ECM matrix degrading enzymes(MMP-13,MMP-3),cartilage metabolism markers(CTX-Ⅱ,COMP),and inflammatory mediators(COX-2,INOS,IL-1βand TNF-α)expression,and promoted collagenⅡsynthesis.Both modeling methods resulted in cartilage damage.In particular,the OA model constructed by ACLT+PMMx method in rats had obvious joint damage,which was favorable to investigate the degree of cartilage structural damage.GC attenuated cartilage pathological changes,pain severity and inflammatory response in the

关 键 词：银杏内酯C 骨关节炎 动物模型 关节疼痛 病理变化 基质降解 炎症介质 大鼠 

分 类 号：S857.16[农业科学—临床兽医学]