低浓度木瓜蛋白酶诱导兔早期膝骨关节炎滑膜炎症的时间曲线  

Synovial inflammation of a rabbit model of early-stage knee osteoarthritis induced by low concentration of papain at different time points

作　　者：张康乐 郭珈宜[2] 刘源[3] 范仪铭 高山[4] 李峰[2] 郭艳幸[2] Zhang Kang-le;Guo Jia-yi;Liu Yuan;Fan Yi-ming;Gao Shan;Li Feng;Guo Yan-xing(Mingguang Hospital of Traditional Chinese Medicine, Chuzhou 239400, Anhui Province, China;Luoyang Orthopedic Hospital of Henan Province, Luoyang 471000, Henan Province, China;Henan University of Chinese Medicine, Zhengzhou 450000,Henan Province, China;Hunan University of Chinese Medicine, Changsha 410000, Hunan Province, China)

机构地区：[1]明光市中医院,安徽省滁州市239400 [2]河南省洛阳正骨医院,河南省洛阳市471000 [3]河南中医药大学,河南省郑州市450000 [4]湖南中医药大学,湖南省长沙市410000

出　　处：《中国组织工程研究》2017年第36期5787-5792,共6页Chinese Journal of Tissue Engineering Research

基　　金：河南省科技厅项目(112102310008);国家中医药管理局"平乐郭氏正骨流派传承工作室"建设项目([2012]228);河南省中医药管理局"河南省中医临床学科领军人才培育计划"项目(HNZYLJ20131009)~~

摘　　要：背景:膝关节滑膜炎症在早期膝骨关节炎的发生发展中起重要作用。目的:比较低浓度木瓜蛋白酶不同诱导时间下兔膝骨关节炎滑膜炎症的变化,为研究膝关节滑膜炎提供数据支持。方法:将24只新西兰大耳白兔随机分为4组,分别在第1,4,7天右膝关节注入2%的木瓜蛋白酶和0.03 mol/L L-半胱氨酸混合液0.5 m L,在末次注射后第1,2,3周将兔子分批处死,空白对照组在第3周处死,记录兔膝关节局部皮温和周径,并取滑膜及髌下脂肪垫组织行病理学观察及酶联免疫吸附测定。结果与结论:(1)在造模后第1周有大量关节积液,膝关节局部皮温及周径均高于第2,3周;(2)滑膜组织中白细胞介素1、肿瘤坏死因子α、基质金属蛋白酶13浓度在第1,2,3周均高于空白组,且第1周时浓度最高,第2,3周差异无显著性意义;(3)滑膜组织形态学显示,第1,2,3周滑膜组织均增生、变厚,有炎性细胞浸润,随着造模时间的延长,滑膜组织中血管增生明显增加;(4)说明低浓度木瓜蛋白酶和0.03 mol/L L-半胱氨酸混合在1周内能形成兔膝关节滑膜炎症,并产生大量关节积液,随时间增加滑膜组织增厚、血管增生明显,关节积液减少。BACKGROUND:Synovitis plays an important role in the occurrence and development of early knee osteoarthritis.OBJECTIVE:To compare synovial inflammation in a rabbit mode of knee osteoarthritis induced by injecting low concentration of papain at different time points,thus providing reference for the study on synovitis in knee osteoarthritis.METHODS:Twenty-four New Zealand white rabbits were divided randomly into four groups,and received the injection of0.5mL mixture of2%papain with0.03mol/L L-cysteine into the right knee at1,4and7days,respectively.The model rabbits were respectively sacrificed at1,2and3weeks after the last injection,and the rabbits in the blank control group were killed at3weeks.The local skin temperature and circumference of the knee were recorded,and the synovium and infrapatellar fat pad were separated from the right knees for histopathological observation and ELSA.RESULTS AND CONCLUSION:At the1st week after modeling,joint effusion was significantly increased,local skin temperature and circumference of knee joint were higher than those at the2nd,and3rd weeks.The levels of interleukin-1,tumor necrosis factor-αand matrix metalloproteinase-13in the synovium in the three experimental groups were higher than those in the blank control group at1,2and3weeks after modeling;the levels peaked in the1st week,but no significant fluctuation appeared in the2nd and3rd weeks.There were synovial tissue hyperplasia,thickening,and inflammatory cell infiltration in the1st,2nd and3rd weeks,and the proliferation of synovial tissue increased significantly with time.These findings indicate that the intra-articular injection of low concentration of papain and0.03mol/L L-cysteine mixtures contributes to a rabbit model of knee synovial inflammation within1week,with significantly joint effusion.However,significant synovial tissue thickening and vascular hyperplasia are observed;meanwhile,the joint effusion is decreased obviously.

关 键 词：组织构建 骨组织工程 膝关节 骨关节炎 滑膜炎症 木瓜蛋白酶 动物模型 

分 类 号：R318[医药卫生—生物医学工程]