人脐带间充质干细胞移植对胶原诱导关节炎大鼠软骨寡聚基质蛋白的影响
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摘要
背景
类风湿关节炎(rheumatoid arthritis,RA)是一种高度致残的自身免疫性疾病，炎性细胞因子在放大全身免疫紊乱和关节局部破坏中发挥很重要的作用，以软骨寡聚基质蛋白(cartilage oligomeric matrix protein,COMP)等为著，最终导致周围关节的慢性、对称性、侵蚀性关节炎以及关节外血管炎的表现。本课题通过人脐带间充质干细胞（humanumbilicalcord derived-mesenchymal stem cells,hUC-MSCs）尾静脉移植从细胞因子的角度探讨其在胶原诱导性关节炎大鼠（collagen induced arthritis,CIA）中可能的免疫修复和免疫调节的作用机制。
目的
本研究通过观察hUC-MSCs移植治疗动物模型CIA，观察移植前后的关节症状和炎性细胞因子COMP水平在滑膜和血清中的表达，探讨hUC-MSCs移植对COMP可能的调节作用机制。
方法
1.饲养SD大鼠，间隔两周分别给予两次皮内注射牛Ⅱ型胶原和弗氏完全佐剂混合液，制造CIA模型；
2.将40只大鼠随机分为4组：空白对照组、CIA对照组、MSCs治疗组、MTX治疗组；
3.分四个时点观察各组CIA大鼠症状（包括大体观、关节炎指数、关节肿胀程度）、影像病理学改变，于不同时点对各组大鼠采血，测定血清COMP的水平。
结果
1.通过症状、影像病理学判断，40只接受牛Ⅱ型胶原和弗氏完全佐剂混合液致敏的大鼠，发生对称性多关节炎的大鼠有33只，总体造模成功率83%。
2.通过对关节炎指数、关节肿胀程度重复测量数据的方差分析和观察影像病理学改变，证实造模组比空白对照组有明显增高、破坏；甲氨蝶呤治疗组与MSCs移植治疗组CIA大鼠关节症状改善较为明显。
3.通过对各组大鼠血清中COMP数据进行分析得出及MSCs移植治疗对CIA大鼠COMP水平有抑制作用。
结论
1．MSCs移植治疗可减轻关节炎症状。
2. MSCs移植明显下调CIA大鼠关节滑膜和血清COMP的表达水平。
BackgrounBackground
Rheumatoid arthritis (RA) is a highly disabling autoimmune disease. Inflammatory cytokinesplay an important role in enlarging systemic immunologic dysfunction and local joint destroy.COMP is representative cytokines, eventually leading to chronic, symmetrical, erosive arthritisof peripheral joints and performance of extra-articular vasculitis. This topic was designed bymesenchymal human umbilicalcord derived-mesenchyma stem cells transplantation from the tailvein, to investigate its possible mechanisms in immune recovery and immunomodulation in CIArats
Objective
To observe the treatment of hUC-MSCs transplantation on animal models of CIA, to observejoint symptoms before and after transplantation, and expression of COMP levels in synovial andserum. To investigate the possible regulation mechanism of hUC-MSCs transplantationon.COMP.
Methods
1. SD rats were raised，and respectily given bovine collagen typeⅡand complete Freundadjuvant mixture by endermic injection for two times every tow week., CIA rats were made.
2. The 40 rats were randomly divided into 4 groups: control group, CIA control group, MSCstreatment group, MTX treatment group;
3. Observed symptoms (including the general concept, arthritis index, swelling joint) and thechanges of pathology images on four time points in CIA rats,.Took blood of rats and detected thelevel of serum COMP at different time points.
Results
1. Through the symptoms, pathology images，33 rats occured symmetric polyarthritis in 40 ratsreceived bovine collagen typeⅡand mixture of Freund's complete adjuvant sensitized.Theoverall rate of modeling success was 83% .
2. By variance analysis of arthritis index, repeated measures of swelling joint data and observedchanges of image pathological ,we confirmed the model group had significantly higher damagethan the control; Joint symptoms improved more significantly in the treatment group ofmethotrexate and the treatment group of MSCs transplantation.
3. Through analyzing the serum levels of COMP in every groups,we found that MSCs transplantation inhibited the level of COMP in CIA rat.
conclusioconclusion
1. MSCs transplantation can reduce arthritis symptoms.
2. MSCs transplantation significantly decreased the expression levels of synovial and serumCOMP in CIA rat.
类风湿关节炎(rheumatoid arthritis,RA)是一种高度致残的自身免疫性疾病，炎性细胞因子在放大全身免疫紊乱和关节局部破坏中发挥很重要的作用，以软骨寡聚基质蛋白(cartilage oligomeric matrix protein,COMP)等为著，最终导致周围关节的慢性、对称性、侵蚀性关节炎以及关节外血管炎的表现。本课题通过人脐带间充质干细胞（humanumbilicalcord derived-mesenchymal stem cells,hUC-MSCs）尾静脉移植从细胞因子的角度探讨其在胶原诱导性关节炎大鼠（collagen induced arthritis,CIA）中可能的免疫修复和免疫调节的作用机制。
目的
本研究通过观察hUC-MSCs移植治疗动物模型CIA，观察移植前后的关节症状和炎性细胞因子COMP水平在滑膜和血清中的表达，探讨hUC-MSCs移植对COMP可能的调节作用机制。
方法
1.饲养SD大鼠，间隔两周分别给予两次皮内注射牛Ⅱ型胶原和弗氏完全佐剂混合液，制造CIA模型；
2.将40只大鼠随机分为4组：空白对照组、CIA对照组、MSCs治疗组、MTX治疗组；
3.分四个时点观察各组CIA大鼠症状（包括大体观、关节炎指数、关节肿胀程度）、影像病理学改变，于不同时点对各组大鼠采血，测定血清COMP的水平。
结果
1.通过症状、影像病理学判断，40只接受牛Ⅱ型胶原和弗氏完全佐剂混合液致敏的大鼠，发生对称性多关节炎的大鼠有33只，总体造模成功率83%。
2.通过对关节炎指数、关节肿胀程度重复测量数据的方差分析和观察影像病理学改变，证实造模组比空白对照组有明显增高、破坏；甲氨蝶呤治疗组与MSCs移植治疗组CIA大鼠关节症状改善较为明显。
3.通过对各组大鼠血清中COMP数据进行分析得出及MSCs移植治疗对CIA大鼠COMP水平有抑制作用。
结论
1．MSCs移植治疗可减轻关节炎症状。
2. MSCs移植明显下调CIA大鼠关节滑膜和血清COMP的表达水平。
BackgrounBackground
Rheumatoid arthritis (RA) is a highly disabling autoimmune disease. Inflammatory cytokinesplay an important role in enlarging systemic immunologic dysfunction and local joint destroy.COMP is representative cytokines, eventually leading to chronic, symmetrical, erosive arthritisof peripheral joints and performance of extra-articular vasculitis. This topic was designed bymesenchymal human umbilicalcord derived-mesenchyma stem cells transplantation from the tailvein, to investigate its possible mechanisms in immune recovery and immunomodulation in CIArats
Objective
To observe the treatment of hUC-MSCs transplantation on animal models of CIA, to observejoint symptoms before and after transplantation, and expression of COMP levels in synovial andserum. To investigate the possible regulation mechanism of hUC-MSCs transplantationon.COMP.
Methods
1. SD rats were raised，and respectily given bovine collagen typeⅡand complete Freundadjuvant mixture by endermic injection for two times every tow week., CIA rats were made.
2. The 40 rats were randomly divided into 4 groups: control group, CIA control group, MSCstreatment group, MTX treatment group;
3. Observed symptoms (including the general concept, arthritis index, swelling joint) and thechanges of pathology images on four time points in CIA rats,.Took blood of rats and detected thelevel of serum COMP at different time points.
Results
1. Through the symptoms, pathology images，33 rats occured symmetric polyarthritis in 40 ratsreceived bovine collagen typeⅡand mixture of Freund's complete adjuvant sensitized.Theoverall rate of modeling success was 83% .
2. By variance analysis of arthritis index, repeated measures of swelling joint data and observedchanges of image pathological ,we confirmed the model group had significantly higher damagethan the control; Joint symptoms improved more significantly in the treatment group ofmethotrexate and the treatment group of MSCs transplantation.
3. Through analyzing the serum levels of COMP in every groups,we found that MSCs transplantation inhibited the level of COMP in CIA rat.
conclusioconclusion
1. MSCs transplantation can reduce arthritis symptoms.
2. MSCs transplantation significantly decreased the expression levels of synovial and serumCOMP in CIA rat.
引文
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