东南大学学报（医学版）
東南大學學報（醫學版）
동남대학학보（의학판）
JOURNAL OF SOUTHEAST UNIVERSITY(MEDICAL SCIENCE EDITION)
2015年
4期
514-521
,共8页
胶原诱导性关节炎%骨侵蚀%DKK1%肿瘤坏死因子-α%99锝-亚甲基二磷酸盐
膠原誘導性關節炎%骨侵蝕%DKK1%腫瘤壞死因子-α%99锝-亞甲基二燐痠鹽
효원유도성관절염%골침식%DKK1%종류배사인자-α%99득-아갑기이린산염
collagen-induced arthritis%bone erosion%dickkopf-1%tumor necrosis factor-α%99 Tc-MDP
目的：观察胶原诱导性关节炎（ CIA）大鼠DKK1的表达及99锝－亚甲基二磷酸盐（99 Tc－MDP，商品名：云克）对骨侵蚀的治疗作用，探讨云克治疗骨侵蚀的可能作用机制。方法：建立CIA大鼠模型，分为模型组、甲氨蝶呤（ MTX）组、云克小剂量组、云克大剂量组；通过Larsen评分和病理组织形态学评分评价骨质破坏；ELISA法检测关节液和血清DKK1、肿瘤坏死因子（ TNF）－α水平；免疫组化法检测踝关节区滑膜及软骨的DKK1、TNF－α表达；采用方差分析、t检验和相关分析进行统计学处理。结果：云克干预组和MTX组大鼠骨质破坏，血清和关节液DKK1、TNF－α水平，踝关节区滑膜及软骨DKK1、TNF－α表达均低于模型组（ P＜0．05）；云克干预组骨质破坏、血清和关节液DKK1水平、踝关节区滑膜及软骨DKK1表达低于MTX组（ P＜0．05），但云克组间差异无统计学意义（P＞0．05）；云克干预组和MTX组血清和关节液TNF－α水平、踝关节区滑膜及软骨TNF－α表达组间差异无统计学意义（ P＞0．05）；相关性分析显示模型组及药物干预组大鼠血清和关节液DKK1与TNF－α水平呈正相关（r＝0．439，P＜0．05）。结论：云克可以减轻CIA大鼠骨侵蚀，疗效优于MTX，可能是通过直接降低DKK1或通过抑制TNF－α间接下调DKK1，增强Wnt信号通路保护骨侵蚀。
目的：觀察膠原誘導性關節炎（ CIA）大鼠DKK1的錶達及99锝－亞甲基二燐痠鹽（99 Tc－MDP，商品名：雲剋）對骨侵蝕的治療作用，探討雲剋治療骨侵蝕的可能作用機製。方法：建立CIA大鼠模型，分為模型組、甲氨蝶呤（ MTX）組、雲剋小劑量組、雲剋大劑量組；通過Larsen評分和病理組織形態學評分評價骨質破壞；ELISA法檢測關節液和血清DKK1、腫瘤壞死因子（ TNF）－α水平；免疫組化法檢測踝關節區滑膜及軟骨的DKK1、TNF－α錶達；採用方差分析、t檢驗和相關分析進行統計學處理。結果：雲剋榦預組和MTX組大鼠骨質破壞，血清和關節液DKK1、TNF－α水平，踝關節區滑膜及軟骨DKK1、TNF－α錶達均低于模型組（ P＜0．05）；雲剋榦預組骨質破壞、血清和關節液DKK1水平、踝關節區滑膜及軟骨DKK1錶達低于MTX組（ P＜0．05），但雲剋組間差異無統計學意義（P＞0．05）；雲剋榦預組和MTX組血清和關節液TNF－α水平、踝關節區滑膜及軟骨TNF－α錶達組間差異無統計學意義（ P＞0．05）；相關性分析顯示模型組及藥物榦預組大鼠血清和關節液DKK1與TNF－α水平呈正相關（r＝0．439，P＜0．05）。結論：雲剋可以減輕CIA大鼠骨侵蝕，療效優于MTX，可能是通過直接降低DKK1或通過抑製TNF－α間接下調DKK1，增彊Wnt信號通路保護骨侵蝕。
목적：관찰효원유도성관절염（ CIA）대서DKK1적표체급99득－아갑기이린산염（99 Tc－MDP，상품명：운극）대골침식적치료작용，탐토운극치료골침식적가능작용궤제。방법：건립CIA대서모형，분위모형조、갑안접령（ MTX）조、운극소제량조、운극대제량조；통과Larsen평분화병리조직형태학평분평개골질파배；ELISA법검측관절액화혈청DKK1、종류배사인자（ TNF）－α수평；면역조화법검측과관절구활막급연골적DKK1、TNF－α표체；채용방차분석、t검험화상관분석진행통계학처리。결과：운극간예조화MTX조대서골질파배，혈청화관절액DKK1、TNF－α수평，과관절구활막급연골DKK1、TNF－α표체균저우모형조（ P＜0．05）；운극간예조골질파배、혈청화관절액DKK1수평、과관절구활막급연골DKK1표체저우MTX조（ P＜0．05），단운극조간차이무통계학의의（P＞0．05）；운극간예조화MTX조혈청화관절액TNF－α수평、과관절구활막급연골TNF－α표체조간차이무통계학의의（ P＞0．05）；상관성분석현시모형조급약물간예조대서혈청화관절액DKK1여TNF－α수평정정상관（r＝0．439，P＜0．05）。결론：운극가이감경CIA대서골침식，료효우우MTX，가능시통과직접강저DKK1혹통과억제TNF－α간접하조DKK1，증강Wnt신호통로보호골침식。
Objective: To observe the expression of dickkopf-1(DKKl) and the effects of 99Tc-MDP on bone erosion in collagen-induced arthritis(CIA) rats, and to explore the possible treatment mechanism of 99Tc-MDP. Methods:The CIA models were established by subcutaneous injection with typeⅡ collagen and complete Freud’s adjuvant to rats.CIA rats were randomly divided into 4 groups:model group, methotrexate( MTX) group, low dose <br> 99 Tc-MDP group, and high dose 99 Tc-MDP group.Destruction of bone were assessed by Larsen score and histopathological score.The synovial fluid and serum levels of DKK1 and TNF-αwere tested by ELISA.The synovium and cartilage of ankle joints expressions of DKK1 and TNF-αwere tested by immunohistochemistry.T test, analysis of variance, and correlation analysis were used for statistic analysis.Results:Compared with model group, destruction of bone, synovial fluid and serum levels of DKK1 and TNF-α, and synovium and cartilage of ankle joints expressions of DKK1 and TNF-αin drugs intervention groups were significantly decreased( P<0.05) . Destruction of bone, synovial fluid and serum levels of DKK1, and synovium and cartilage of ankle joints expressions of DKK1 in 99Tc-MDP intervention groups were notably lower than those in MTX group(P<0.05), and the indexes in both 99Tc-MDP groups illustrated no significant difference(P>0.05).Moreover, synovial fluid and serum levels of TNF-α, and synovium and cartilage of ankle joints expressions of TNF-αin MTX group and both 99 Tc-MDP groups demonstrated no significant differences( P>0.05) .Correlation analysis showed that synovial fluid and serum levels of DKK1 and TNF-αin model and drugs intervention groups were positively correlated( r=0.439,P<0.05).Conclusion: 99Tc-MDP can reduce bone erosion of CIA rats, and the therapeutic effect is better than MTX, probably by reducing the DKK1 directly or inhibiting DKK1 to lower down TNF-αindirectly, thereby enhancing the wnt signaling pathway to protect bone erosion.
