NOD2、NLRP3在石膏关节制动法建立兔膝骨性关节炎模型关节软骨中的表达

Expression of NOD2 and NLRP3 in the articular cartilage of a rabbit model of osteoarthritis established by arthrorisis using plaster cast

背景:NOD样受体在抵抗外部病原微生物、自身的非细菌性炎症反应以及自身免疫反应过程的起始阶段中起着重要的作用,而NLRP3和NOD2是NOD样受体家族中具有代表性的两种重要蛋白。目的:观察兔膝骨性关节炎模型中软骨细胞NOD2、NLRP3表达。方法:30只新西兰大白兔随机分为6组:实验组分别设置2,4,6,8,10周组,采用石膏关节制动法建立兔左侧膝关节膝骨性关节炎模型,分别于术后2,4,6,8,10周处死对应实验组兔子;对照组不做任何处理,于第10周处死兔子5只。留取所有兔子的左股骨远端关节软骨标本,进行番红固绿染色,用Mankin’s法进行关节病理评分,免疫组织化学检测关节软骨中NOD2、NLRP3的表达水平。结果与结论:(1)Mankin’s评分结果显示:实验组病理评分显著高于对照组(P<0.01),而且随着造模时间的推移各组间的Mankin’s评分增加,均有显著性差异(P<0.01);(2)免疫组织化学结果表明:NLRP3、NOD2在软骨细胞中的表达含量随着造模时间的推移也显著增高(P<0.01);(3)结果说明,NOD2、NLRP3在软骨细胞中的表达与膝骨性关节炎的病理变化程度呈正相关性,可能是通过促进细胞凋亡进而加速膝骨性关节炎的发生发展。

BACKGROUND:Nucleotide-binding oligomerization domain(NOD)-like receptor plays an important role against inflammatory responses caused by pathogens and non-pathogens,as well as in the initial stage of autoimmune response.Meanwhile,NOD2 and NOD-like receptor protein 3(NLRP3)are the representative proteins of NOD-like receptor family.OBJECTIVE:To detect the expression of NOD2 and NLRP3 in a rabbit model of osteoarthritis.METHODS:Thirty New Zealand rabbits were randomly divided into six groups(n=5 per group),including five experimental groups(2,4,6,8 and 10 weeks)and one control group.The model of osteoarthritis was established by fixing the left knee joints using plaster cast,and were sacrificed at postoperative 2,4,6,8 and 10 weeks.The controls received no intervention,and were killed at 10 weeks postoperatively.The left distal femur articular cartilage was taken for safranin-fast green staining.The pathological changes were evaluated by Mankin’s scores,and the expression levels of NOD2 and NLRP3 were detected by immunohistochemistry.RESULTS AND CONCLUSION:The Mankin’s scores in the experimental groups were significantly higher than those in the control group(P<0.01).Moreover,the scores in the experimental groups were significantly increased with time(P<0.01).The expression levels of NOD2 and NLRP3 in the chondrocytes were also increased with time(P<0.01).These results indicate that the expresison of NOD2 and NLRP3 in the cartilage cells is positively correlated with the pathological changes of osteoarthritis,which may be through promoting apoptosis in cartilage cells,thus accelerating the development of osteoarthritis.