舒尼替尼干预大鼠膝骨关节炎的实验研究  

An experimental study of sunitinib for prevention of knee osteoarthritis in rats

作　　者：王金杰 俞倩丽 范魏魏 庄汝杰[2] 

机构地区：[1]浙江中医药大学,浙江杭州310053 [2]浙江省中医院,浙江杭州310006

出　　处：《中医正骨》2018年第1期1-5,共5页The Journal of Traditional Chinese Orthopedics and Traumatology

基　　金：2014年浙江省重大科技专项计划项目(2014C03038);2016年浙江中医药科技计划项目(2016ZA085)

摘　　要：目的:探讨舒尼替尼对大鼠膝骨关节炎(knee osteoarthritis,KOA)的影响。方法:选取32只雄性SD大鼠,随机分为空白组、模型组、4周治疗组及8周治疗组,每组8只。除空白组外,其余3组大鼠均采用木瓜蛋白酶进行KOA造模。造模完成后,空白组大鼠正常喂养;4周治疗组和8周治疗组大鼠按照1 mg·kg^(-1)以舒尼替尼灌胃,每天1次,2组分别持续干预4周和8周;模型组大鼠每天以同等体积生理盐水灌胃。药物干预结束后处死各组大鼠,分别进行膝关节MRI检查、关节液血管内皮生长因子(vascular endothelial growth factor,VEGF)和基质金属蛋白酶(matrix metalloproteinase,MMP)-13水平测定、膝关节组织病理学观察。结果:(1)膝关节MRI检查结果。大鼠膝关节矢状位MRI显示,空白组大鼠膝关节结构完整,关节表面有完整的软骨,表面光滑,软骨与骨组织连接紧密,软骨下无炎症及囊性病变,软骨下骨无磨损、无骨赘;模型组大鼠膝关节结构明显破坏,表面软骨明显磨损,特别是胫骨平台有明显软骨及软骨下骨破损,软骨下有囊性病变;4周治疗组大鼠膝关节结构基本完整,软骨略粗糙,但胫骨平台下仍见软骨下炎症及软骨下骨破损,软骨下存在囊性病变;8周治疗组大鼠膝关节结构完整,软骨完整光滑,软骨下骨无明显破损,软骨下无明显囊性病变,但软骨下仍有一定程度的炎症。(2)膝关节液VEGF、MMP-13水平测定结果。4组大鼠关节液VEGF水平比较,差异有统计学意义[(152.26±31.17)pg·m L^(-1),(237.95±69.10)pg·m L^(-1),(168.43±47.47)pg·m L^(-1),(136.75±27.48)pg·m L^(-1),F=14.575,P=0.000]。模型组关节液VEGF水平高于空白组、4周治疗组和8周治疗组(P=0.000,P=0.000,P=0.000);空白组与4周治疗组、8周治疗组比较,差异均无统计学意义(P=0.332,P=0.181);4周治疗组与8周治疗组比较,差异无统计学意义(P=0.060)。4组大鼠关节液MMP-13水平比较,差异有统计学意义[(60.85±13.70)pgObjective: To explore the effect of sunitinib on knee osteoarthritis( KOA) in rats. Methods: Thirty-two male SD rats were selected and were randomly divided into blank group,model group,4-week treatment group and 8-week treatment group,8 cases in each group. The KOA rat models were created in model group,4-week treatment group and 8-week treatment group by using papain,while the rats in blank group were not given any intervention. After the modeling,the rats in blank group were fed normally,and the rats in 4-week treatment group and 8-week treatment group were intragastric administrated with sunitinib( 1 mg/kg),once a day for consecutive 4 and 8 weeks respectively; while the rats in model group were intragastric administrated with the same dose of normal saline everyday. After the end of drug intervention,the rats in each group were executed. MRI examination and histopathological observation on knee joint and determination of knee joint fluid level of vascular endothelial growth factor( VEGF) and matrix metalloproteinase( MMP)-13 were performed on rats in each group. Results: The results of sagittal MRI examination of knee joint showed that in blank group( 1) the structure of knee-joint was complete;( 2) the articular surface was smooth and the articular cartilage was intact;( 3) the cartilage tissue was closely connected with bone tissue;( 4) no inflammation and cystis degeneration were found under cartilage;( 5) no abrasion and osteophyte were found in subchondral bone. The sagittal MRI images also showed that in model group( 1) the structure of knee-joint was obviously damaged;( 2) the superne cartilage was obviously worn;( 3) obvious damages of cartilage and subchondral bone and obvious subchondral cystis degeneration were found under the tibial plateau. In 4-week treatment group,the structure of knee-joint was basically intact and the cartilage was roughish,while subchondral inflammation,bone damages and cystis degeneration were found under the tibial plateau. In 8-week treatment group,the structure of knee-

关 键 词：骨关节炎 膝 血管内皮生长因子类 基质金属蛋白酶13 舒尼替尼 动物实验 

分 类 号：R965[医药卫生—药理学]