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[1]王金杰,俞倩麗,范魏魏,等.舒尼替尼干預大鼠膝骨關(guān)節(jié)炎的實驗研究[J].中醫(yī)正骨,2018,30(01):1-5.
　WANG Jinjie,YU Qianli,FAN Weiwei,et al.An experimental study of sunitinib for prevention of knee osteoarthritis in rats[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2018,30(01):1-5.
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舒尼替尼干預大鼠膝骨關(guān)節(jié)炎的實驗研究()
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《中醫(yī)正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第30卷
期數(shù):
2018年01期
頁碼:
1-5
欄目:
基礎(chǔ)研究
出版日期:
2018-01-20

文章信息/Info

Title:
An experimental study of sunitinib for prevention of knee osteoarthritis in rats
作者:
王金杰1; 俞倩麗1; 范魏魏1; 莊汝杰2
1.浙江中醫(yī)藥大學,浙江 杭州 310053; 2.浙江省中醫(yī)院,浙江 杭州 310006
Author(s):
WANG Jinjie1; YU Qianli1; FAN Weiwei1; ZHUANG Rujie2
1.Zhejiang Chinese Medical University,Hangzhou 310053,Zhejiang,China 2.Zhejiang Provincial Hospital of Traditional Chinese Medicine,Hangzhou 310006,Zhejiang,China
關(guān)鍵詞:
骨關(guān)節(jié)炎; 膝;  血管內(nèi)皮生長因子類;  基質(zhì)金屬蛋白酶13;  舒尼替尼;  動物實驗
Keywords:
Keywords osteoarthritis; knee;  vascular endothelial growth factors;  matrix metalloproteinase 13;  sunitinib;  animal experimentation
摘要:
目的:探討舒尼替尼對大鼠膝骨關(guān)節(jié)炎(knee osteoarthritis,KOA)的影響。方法:選取32只雄性SD大鼠,隨機分為空白組、模型組、4周治療組及8周治療組,每組8只。除空白組外,其余3組大鼠均采用木瓜蛋白酶進行KOA造模。造模完成后,空白組大鼠正常喂養(yǎng); 4周治療組和8周治療組大鼠按照1 mg·kg-1以舒尼替尼灌胃,每天1次,2組分別持續(xù)干預4周和8周; 模型組大鼠每天以同等體積生理鹽水灌胃。藥物干預結(jié)束后處死各組大鼠,分別進行膝關(guān)節(jié)MRI檢查、關(guān)節(jié)液血管內(nèi)皮生長因子(vascular endothelial growth factor,VEGF)和基質(zhì)金屬蛋白酶(matrix metalloproteinase,MMP)-13水平測定、膝關(guān)節(jié)組織病理學觀察。結(jié)果:①膝關(guān)節(jié)MRI檢查結(jié)果。大鼠膝關(guān)節(jié)矢狀位MRI顯示,空白組大鼠膝關(guān)節(jié)結(jié)構(gòu)完整,關(guān)節(jié)表面有完整的軟骨,表面光滑,軟骨與骨組織連接緊密,軟骨下無炎癥及囊性病變,軟骨下骨無磨損、無骨贅; 模型組大鼠膝關(guān)節(jié)結(jié)構(gòu)明顯破壞,表面軟骨明顯磨損,特別是脛骨平臺有明顯軟骨及軟骨下骨破損,軟骨下有囊性病變; 4周治療組大鼠膝關(guān)節(jié)結(jié)構(gòu)基本完整,軟骨略粗糙,但脛骨平臺下仍見軟骨下炎癥及軟骨下骨破損,軟骨下存在囊性病變; 8周治療組大鼠膝關(guān)節(jié)結(jié)構(gòu)完整,軟骨完整光滑,軟骨下骨無明顯破損,軟骨下無明顯囊性病變,但軟骨下仍有一定程度的炎癥。②膝關(guān)節(jié)液VEGF、MMP-13水平測定結(jié)果。4組大鼠關(guān)節(jié)液VEGF水平比較,差異有統(tǒng)計學意義[(152.26±31.17)pg·mL-1,(237.95±69.10)pg·mL-1,(168.43±47.47)pg·mL-1,(136.75±27.48)pg·mL-1,F=14.575,P=0.000]。模型組關(guān)節(jié)液VEGF水平高于空白組、4周治療組和8周治療組(P=0.000,P=0.000,P=0.000); 空白組與4周治療組、8周治療組比較,差異均無統(tǒng)計學意義(P=0.332,P=0.181); 4周治療組與8周治療組比較,差異無統(tǒng)計學意義(P=0.060)。4組大鼠關(guān)節(jié)液MMP-13水平比較,差異有統(tǒng)計學意義[(60.85±13.70)pg·mL-1,(94.98±37.63)pg·mL-1,(75.43±20.23)pg·mL-1,(68.54±19.82)pg·mL-1,F=5.686,P=0.002]。模型組關(guān)節(jié)液MMP-13水平高于空白組、4周治療組和8周治療組(P=0.028,P=0.003,P=0.000); 空白組與4周治療組、8周治療組比較,差異均無統(tǒng)計學意義(P=0.098,P=0.242); 4周治療組與8周治療組比較,差異無統(tǒng)計學意義(P=0.431)。③膝關(guān)節(jié)組織病理學觀察結(jié)果。空白組大鼠膝關(guān)節(jié)整體結(jié)構(gòu)完整,軟骨面光滑,無壞死、潰瘍,骨小梁結(jié)構(gòu)、形態(tài)完整; 模型組大鼠膝關(guān)節(jié)有典型的軟骨受損表現(xiàn),軟骨面不光滑,部分軟骨脫失,軟骨細胞排列紊亂,骨小梁不完整; 4周治療組大鼠膝關(guān)節(jié)面較模型組略光滑,軟骨細胞排列尚整齊、分布均勻,骨小梁的結(jié)構(gòu)、形態(tài)較模型組完整,但仍有部分碎裂; 8周治療組大鼠膝關(guān)節(jié)軟骨光滑,軟骨細胞分布均勻、排列整齊,各層次清晰,無明顯細胞簇集現(xiàn)象,潮線完整,骨小梁結(jié)構(gòu)基本完整。結(jié)論:舒尼替尼能通過抑制KOA大鼠膝關(guān)節(jié)VEGF的表達,抑制MMP-13的表達,從而延緩膝關(guān)節(jié)退變,其效果與作用時間有關(guān)。
Abstract:
ABSTRACT Objective: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-joint was intact and the cartilage was complete and smooth,and no obvious subchondral bone damages and subchondral cystis degeneration were found,while some subchondral inflammation was found.There was statistical difference in the level of VEGF in knee joint fluid between the 4 groups(152.26+/-31.17,237.95+/-69.10,168.43+/-47.47,136.75+/-27.48 pg/mL,F=14.575,P=0.000).The level of VEGF in knee joint fluid was higher in model group compared to blank group,4-week treatment group and 8-week treatment group(P=0.000,P=0.000,P=0.000); and there was no statistical difference in the level of VEGF between blank group and 4-week treatment group and between blank group and 8-week treatment group(P=0.332,P=0.181); and there was no statistical difference in the level of VEGF between 4-week treatment group and 8-week treatment group(P=0.060).There was statistical difference in the level of MMP-13 in knee joint fluid between the 4 groups(60.85+/-13.70,94.98+/-37.63,75.43+/-20.23,68.54+/-19.82 pg/mL,F=5.686,P=0.002).The level of MMP-13 in knee joint fluid was higher in model group compared to blank group,4-week treatment group and 8-week treatment group(P=0.028,P=0.003,P=0.000); and there was no statistical difference in the level of MMP-13 between blank group and 4-week treatment group and between blank group and 8-week treatment group(P=0.098,P=0.242); and there was no statistical difference in the level of MMP-13 between 4-week treatment group and 8-week treatment group(P=0.431).The results of histopathological observation on knee joints of rats in blank group showed that(1)the integral structure of the knee joint was complete;(2)the surface of cartilage was smooth without necrosis and ulcer;(3)the structure and morphology of the trabecular bone were complete.The results of histopathological observation on knee joints of rats in model group showed that(1)the knee joint was characterized by typical cartilaginous damage;(2)the surface of cartilage was unsmooth and some of the cartilages were lost;(3)the chondrocytes were disorganized;(4)the trabecular bone was incomplete.In 4-week treatment group,the knee joint surface was slightly smoother compared to model group,and the chondrocytes were regularly arranged and uniformly distributed,and the structure and morphology of the trabecular bone were more complete compared to model group,while some fragments of trabecular bone were still found.In 8-week treatment group,the knee articular cartilage was smooth and the chondrocytes uniformly distributed and regularly arranged with clear layers; no chondrocytes clustered together,and the tidal line was complete and the structure of trabecular bone was basically complete.Conclusion:Sunitinib can inhibit the expression of MMP-13 through inhibiting the expression of VEGF in knee joints of KOA rat models,which may be the mechanisms of action for delaying knee joint degeneration,and its effect is related to the action time.

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備注/Memo

備注/Memo:
基金項目:2014年浙江省重大科技專項計劃項目(2014C03038); 2016年浙江中醫(yī)藥科技計劃項目(2016ZA085) 通訊作者:莊汝杰 E-mail:[email protected]
更新日期/Last Update: 2018-06-02