本文選題：膠原誘導(dǎo)性關(guān)節(jié)炎 + 骨侵蝕　； 參考：《東南大學(xué)》2015年碩士論文

【摘要】：目的：觀察膠原誘導(dǎo)性關(guān)節(jié)炎(CIA)大鼠血清和關(guān)節(jié)液DKK1、TNF-α的水平、踝關(guān)節(jié)區(qū)滑膜及軟骨DKK1、TNF-α的表達(dá),探討CIA大鼠血清及關(guān)節(jié)液DKKl與TNF-α的相關(guān)性及99Tc-MDP治療骨侵蝕的可能作用機(jī)制。方法：建立CIA大鼠模型,分為模型組、MTX組、99Tc-MDP小劑量組、99Tc-MDP大劑量組；通過(guò)Larsen評(píng)分和病理組織形態(tài)學(xué)評(píng)分評(píng)價(jià)骨侵蝕：ELISA法檢測(cè)關(guān)節(jié)液和血清DKK1、TNF-α水平；免疫組化法檢測(cè)踝關(guān)節(jié)區(qū)滑膜及軟骨的DKK1、TNF-α表達(dá)；采用方差分析、t檢驗(yàn)和相關(guān)分析進(jìn)行統(tǒng)計(jì)學(xué)處理。結(jié)果：CIA大鼠的骨侵蝕、血清及關(guān)節(jié)液DKK1、TNF-α的水平、踝關(guān)節(jié)區(qū)滑膜及軟骨DKK1、TNF-α的表達(dá)均顯著高于正常對(duì)照組(P0.05)。MTX組和99Tc-MDP大小劑量組大鼠的骨侵蝕、血清和關(guān)節(jié)液DKK1、TNF-α的水平、踝關(guān)節(jié)區(qū)滑膜及軟骨DKK1、TNF-α的表達(dá)均顯著低于模型組(P0.05), 99Tc-MDP大小劑量組血清DKK1的水平均于給藥1周后降低(P0.05), MTX組血清DKK1的水平于給藥2周后降低(P0.05),MTX組、99Tc-MDP大小劑量組血清TNF-α水平均于給藥1周后降低(P0.05)o 99Tc-MDP大小劑量組大鼠的骨侵蝕、血清和關(guān)節(jié)液DKKl的水平、踝關(guān)節(jié)區(qū)滑膜及軟骨DKK1的表達(dá)均低于MTX組(P0.05),但99Tc-MDP大小劑量組組間比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05); 99Tc-MDP大小劑量組和MTX組血清和關(guān)節(jié)液TNF-α的水平、踝關(guān)節(jié)區(qū)滑膜及軟骨TNF-α的表達(dá)組間比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)；相關(guān)性分析顯示模型組及藥物干預(yù)組大鼠血清和關(guān)節(jié)液DKK1與TNF-α的水平呈正相關(guān)(r=0.439,P0.05)結(jié)論：CIA大鼠血清及關(guān)節(jié)液DKK1、TNF-α的水平、踝關(guān)節(jié)區(qū)滑膜及軟骨DKK1、TNF-a的表達(dá)均顯著高于正常對(duì)照組,提示DKK1和TNF-α可能參與了CIA大鼠骨侵蝕的發(fā)生發(fā)展；99Tc-MDP大小劑量組和MTX組均可顯著降低CIA大鼠血清及關(guān)節(jié)液DKK1、TNF-α的水平和踝關(guān)節(jié)區(qū)滑膜及軟骨DKK1、TNF-α的表達(dá);99Tc-MDP大小劑量組在降低CIA大鼠血清及關(guān)節(jié)液DKK1水平和踝關(guān)節(jié)區(qū)滑膜和軟骨DKK1表達(dá)方面優(yōu)于MTX組；相關(guān)性分析顯示CIA大鼠血清和關(guān)節(jié)液DKK1與TNF-α水平呈正相關(guān),提示CIA大鼠血清和關(guān)節(jié)液DKK1的水平可能與TNF-α的誘導(dǎo)有關(guān)。
[Abstract]:Objective: to observe the level of DKK1TNF- 偽 in serum and joint fluid of rats with collagen-induced arthritis (CIA-C) and the expression of DKK1TNF- 偽 in synovial and chondrocytes of ankle, and to investigate the relationship between DKKl and TNF- 偽 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- 偽 in joint fluid and serum were evaluated by Larsen score and histopathological score. The expression of DKK1 TNF- 偽 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- 偽. Results the bone erosion, serum and joint fluid DK1TNF- 偽 levels, and the expression of DKK1TNF- 偽 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- 偽 were significantly higher than those in the control group. The expression of DKK1TNF- 偽 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- 偽 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- 偽 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- 偽 in synovium and cartilage between the two groups, and the correlation analysis showed that the levels of serum and joint fluid DKK1 and TNF- 偽 in model group and drug intervention group were positively correlated with the level of TNF- 偽. 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- 偽 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- 偽 in serum and articular fluid of CIA rats and the expression of TNF- 偽 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- 偽, suggesting that the levels of DKK1 in serum and joint fluid of CIA rats might be related to the induction of TNF- 偽.
【學(xué)位授予單位】：東南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R684.3

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