胶原诱导性关节炎大鼠DKK1和TNF-α表达的相关性研究及药物干预

发布时间：2018-05-03 15:22

本文选题：胶原诱导性关节炎 + 骨侵蚀　；参考：《东南大学》2015年硕士论文

【摘要】：目的：观察胶原诱导性关节炎(CIA)大鼠血清和关节液DKK1、TNF-α的水平、踝关节区滑膜及软骨DKK1、TNF-α的表达,探讨CIA大鼠血清及关节液DKKl与TNF-α的相关性及99Tc-MDP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、MTX组、99Tc-MDP小剂量组、99Tc-MDP大剂量组；通过Larsen评分和病理组织形态学评分评价骨侵蚀：ELISA法检测关节液和血清DKK1、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：CIA大鼠的骨侵蚀、血清及关节液DKK1、TNF-α的水平、踝关节区滑膜及软骨DKK1、TNF-α的表达均显著高于正常对照组(P0.05)。MTX组和99Tc-MDP大小剂量组大鼠的骨侵蚀、血清和关节液DKK1、TNF-α的水平、踝关节区滑膜及软骨DKK1、TNF-α的表达均显著低于模型组(P0.05), 99Tc-MDP大小剂量组血清DKK1的水平均于给药1周后降低(P0.05), MTX组血清DKK1的水平于给药2周后降低(P0.05),MTX组、99Tc-MDP大小剂量组血清TNF-α水平均于给药1周后降低(P0.05)o 99Tc-MDP大小剂量组大鼠的骨侵蚀、血清和关节液DKKl的水平、踝关节区滑膜及软骨DKK1的表达均低于MTX组(P0.05),但99Tc-MDP大小剂量组组间比较差异无统计学意义(P0.05); 99Tc-MDP大小剂量组和MTX组血清和关节液TNF-α的水平、踝关节区滑膜及软骨TNF-α的表达组间比较差异无统计学意义(P0.05)；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的水平呈正相关(r=0.439,P0.05)结论：CIA大鼠血清及关节液DKK1、TNF-α的水平、踝关节区滑膜及软骨DKK1、TNF-a的表达均显著高于正常对照组,提示DKK1和TNF-α可能参与了CIA大鼠骨侵蚀的发生发展；99Tc-MDP大小剂量组和MTX组均可显著降低CIA大鼠血清及关节液DKK1、TNF-α的水平和踝关节区滑膜及软骨DKK1、TNF-α的表达;99Tc-MDP大小剂量组在降低CIA大鼠血清及关节液DKK1水平和踝关节区滑膜和软骨DKK1表达方面优于MTX组；相关性分析显示CIA大鼠血清和关节液DKK1与TNF-α水平呈正相关,提示CIA大鼠血清和关节液DKK1的水平可能与TNF-α的诱导有关。
[Abstract]:Objective: to observe the level of DKK1TNF- 伪 in serum and joint fluid of rats with collagen-induced arthritis (CIA-C) and the expression of DKK1TNF- 伪 in synovial and chondrocytes of ankle, and to investigate the relationship between DKKl and TNF- 伪 in serum and articular fluid of CIA rats and the possible mechanism of 99Tc-MDP in the treatment of bone erosion. Methods: the CIA rat model was established and divided into two groups: the model group was divided into two groups: the high dose group of low dose group (99 Tc-MDP), the high dose group of 99Tc-MDP, and the level of DKK1 TNF- 伪 in joint fluid and serum were evaluated by Larsen score and histopathological score. The expression of DKK1 TNF- 伪 in synovium and cartilage of ankle joint was detected by immunohistochemical method, and the variance analysis and correlation analysis were used to analyze the expression of TNF- 伪. Results the bone erosion, serum and joint fluid DK1TNF- 伪 levels, and the expression of DKK1TNF- 伪 in synovium and cartilage in the ankle area were significantly higher than those in the normal control group (P 0.05) and 99Tc-MDP groups, and the levels of serum and joint fluid DK1TNF- 伪 were significantly higher than those in the control group. The expression of DKK1TNF- 伪 in synovial membrane and cartilage of ankle joint was significantly lower than that in model group (P 0.05). The level of serum DKK1 in large and small dose groups of 99Tc-MDP decreased after 1 week of administration. The level of serum DKK1 in MTX group was lower than that in group B 2 weeks after administration. The level of TNF- 伪 decreased the bone erosion of rats in the dose of P0.05o 99Tc-MDP one week after administration. The levels of DKKl in serum and joint fluid, the expression of DKK1 in synovium and cartilage in ankle joint area were lower than those in MTX group, but there was no significant difference between 99Tc-MDP group and 99Tc-MDP group, and the level of TNF- 伪 in serum and articular fluid in 99Tc-MDP group and MTX group was lower than that in MTX group. There was no significant difference in the expression of TNF- 伪 in synovium and cartilage between the two groups, and the correlation analysis showed that the levels of serum and joint fluid DKK1 and TNF- 伪 in model group and drug intervention group were positively correlated with the level of TNF- 伪. The expression of TNF-a in synovium and cartilage of ankle joint was significantly higher than that in normal control group. These results suggest that DKK1 and TNF- 伪 may be involved in the occurrence and development of bone erosion in CIA rats. Both the large dose group of 99Tc-MDP and the group of MTX can significantly decrease the level of DKK1TNF- 伪 in serum and articular fluid of CIA rats and the expression of TNF- 伪 in synovial and cartilage of the ankle. The level of DKK1 in serum and joint fluid and the expression of DKK1 in synovium and cartilage of CIA rats were lower than those in MTX group. Correlation analysis showed that the levels of DKK1 in serum and joint fluid of CIA rats were positively correlated with the levels of TNF- 伪, suggesting that the levels of DKK1 in serum and joint fluid of CIA rats might be related to the induction of TNF- 伪.
【学位授予单位】：东南大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R684.3

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