本文關(guān)鍵詞： 骨關(guān)節(jié)炎 強力霉素 IL-1 uPA MMPs-3 NO NOS　出處：《石河子大學(xué)》2010年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:研究關(guān)節(jié)腔內(nèi)注射強力霉素對制動兔骨關(guān)節(jié)炎模型膝關(guān)節(jié)退變的影響,探討其作用機制。 方法：48只新西蘭大白兔隨機分成止常組6只及實驗組42只,試驗組左膝關(guān)節(jié)伸直位石膏固定4周隨機選取6只(石膏固定4周組)處死左膝關(guān)節(jié)取材證實造模成功后剩余36只拆除石膏制成骨關(guān)節(jié)炎模型,隨機分為治療組、陰性對照組和模型對照組,治療組每日給予1.33%的強力霉素0.3毫升左膝關(guān)節(jié)腔內(nèi)注射,陰性對照組每日給予生理鹽水0.3毫升左膝關(guān)節(jié)腔注射,模型對照組不做處理,于4周及8周處死取材。觀察指標包括關(guān)節(jié)軟骨大體形態(tài),軟骨Mankin's評分,關(guān)節(jié)液一氧化氮(NO)及一氧化氮合酶(NOS)活性,軟骨細胞基質(zhì)金屬蛋白酶-3(MMP-3)、尿激酶型纖溶酶原激活物(uPA)表達及滑膜細胞白介素-1(IL-1)表達。 結(jié)果：(1)與正常對照組比較,石膏固定4周組軟骨表面有潰瘍形成,Mankin's評分明顯高于正常對照組,軟骨uPA、MMPs-3活性及滑膜IL-1活性均較高,關(guān)節(jié)液NO含量及NOS活性也高與正常對照組(P0.05)；(2)與石膏固定4周組比較,4周模型對照組,Mankin's評分明顯增高(P0.05),軟骨uPA、MMPs-3活性、滑膜IL-1活性及關(guān)節(jié)液NO含量及NOS活性較高(P0.05),8周時增加更加明顯(P0.05)；(3)與4周模型對照組比較,4周陰性對照組,Mankin's評分明顯增高(P0.05),軟骨uPA、MMPs-3活性、滑膜IL-1活性及關(guān)節(jié)液NO含量及NOS活性較高(P0.05),8周則無明顯差異(P0.05)；(4)與模型對照組及陰性對照組比較,治療組軟骨面光滑,Mankin's評分較低(P0.05),軟骨uPA、MMPs-3舌性、滑膜IL-1活性及關(guān)節(jié)液NO含量及NOS活性均降低(P0.05),但仍高丁正常對照組。 結(jié)論：1、伸直位石膏固定4周可獲得滿意的骨關(guān)節(jié)炎模型,關(guān)節(jié)退變隨病程進展而進展；2、強力霉素關(guān)節(jié)腔內(nèi)注射給藥,可對兔膝骨關(guān)節(jié)炎軟骨退變起明顯緩解作用,其作用機制與軟骨中uPA、MMP-13及滑膜中IL-1表達的抑制,抑制NO的產(chǎn)生及NOS活性等作用有關(guān)。
[Abstract]:Objective: to study the effect of intraarticular injection of doxycycline on degenerative knee joint in immobilization rabbit osteoarthritis model. Methods Forty-eight New Zealand white rabbits were randomly divided into two groups: control group (n = 6) and experimental group (n = 42). In the experimental group, 6 rats (gypsum fixation group) were randomly selected for 4 weeks. The remaining 36 cases were removed to make the osteoarthritis model after the successful establishment of the model. 4 weeks after the left knee joint was fixed with plaster for 4 weeks, the left knee joint was killed to make the osteoarthritis model. They were randomly divided into three groups: the treatment group, the negative control group and the model control group. The treatment group was given 1.33% doxycycline 0.3 ml intraarticular injection into the left knee joint daily. The negative control group was injected with 0.3 ml of normal saline into the left knee joint cavity every day, and the model control group was killed at 4 weeks and 8 weeks. The observed indexes included the gross morphology of articular cartilage. Mankin's score, nitric oxide (no) and nitric oxide synthase (NOS) activity in articular fluid and matrix metalloproteinase-3 (MMP-3) in chondrocytes. The expression of urokinase type plasminogen activator (UPA) and the expression of interleukin-1 (IL-1) in synovial cells. Results compared with the normal control group, the score of cartilage ulcer formation in gypsum fixed group for 4 weeks was significantly higher than that in the normal control group. The cartilage uPA score was significantly higher in the gypsum fixed group than that in the normal control group. The activity of MMPs-3 and IL-1 of synovium were higher, and the content of no and the activity of NOS in joint fluid were also higher than those in normal control group (P 0.05). (2) compared with the gypsum fixed group for 4 weeks, the Mankins score in the control group was significantly higher than that in the control group (P 0.05), and the activity of MMPs-3 in the cartilage uPAM was significantly higher than that in the control group. IL-1 activity, no content and NOS activity in synovial fluid were significantly increased at 8 weeks. 3) compared with the 4-week model control group, the Mankins score in the 4-week negative control group was significantly higher than that in the 4-week model control group, and the activity of uPA-MMPs-3 in cartilage was significantly higher than that in the 4-week model control group. There was no significant difference in IL-1 activity, no content and NOS activity in synovial fluid for 8 weeks. (4) compared with the model control group and the negative control group, the cartilage smooth Mankins score of the treatment group was lower than that of the control group (P 0.05), and the tongue of the cartilage uPA-MMPs-3 was lower than that of the control group. The activity of IL-1 in synovium, no content and NOS activity in synovial fluid decreased (P 0.05), but it was still high in normal control group. Conclusion A satisfactory osteoarthritis model can be obtained after 4 weeks of plaster fixation, and degenerative osteoarthritis develops with the progression of the disease. 2. Intraarticular injection of doxycycline could relieve the degeneration of cartilage in rabbit knee osteoarthritis, and its mechanism was related to the inhibition of uPA-MMP-13 in cartilage and IL-1 expression in synovium. The inhibition of no production and the activity of NOS were related.
【學(xué)位授予單位】：石河子大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2010
【分類號】：R684.3;R-332

【參考文獻】

相關(guān)期刊論文 前10條

1 解志杰,許建中;IGF-I和TGFβ_1對幼年及成年兔關(guān)節(jié)軟骨細胞增殖和代謝的作用[J];第三軍醫(yī)大學(xué)學(xué)報;2001年06期

2 李憶農(nóng);細胞因子與骨關(guān)節(jié)炎[J];中華風(fēng)濕病學(xué)雜志;2000年01期

3 栗占國;骨關(guān)節(jié)炎診治指南(草案)[J];中華風(fēng)濕病學(xué)雜志;2003年11期

4 楊峰,史宗道;用木瓜蛋白酶建立兔顳頜關(guān)節(jié)骨關(guān)節(jié)炎模型的研究[J];華西口腔醫(yī)學(xué)雜志;2002年05期

5 李嘉慶;鄧長財;池中求;鞠中斌;;自由基對類風(fēng)濕關(guān)節(jié)炎軟骨代謝的影響[J];山東醫(yī)藥;2006年23期

6 尚平;賀憲;陳孝銀;才忠民;劉志祥;項旭軍;唐勇;;過伸位和過屈位固定復(fù)制骨性關(guān)節(jié)炎動物模型的比較[J];生物骨科材料與臨床研究;2006年01期

7 李宏宇;安洪;梁斌;李榮祝;田文;韋敏克;;骨水泥阻塞骨干髓腔后遠側(cè)骨干骨密度的變化[J];中國臨床康復(fù);2005年46期

8 何斌;史晨輝;王永明;蔣新忠;孫建華;石輝;;關(guān)節(jié)軟骨破壞與尿激酶型纖溶酶原激活物的影響[J];中國組織工程研究與臨床康復(fù);2007年06期

9 王維山;史晨輝;周卓浩;王永明;董金波;劉維鋼;何斌;管興發(fā);;一側(cè)兔膝關(guān)節(jié)注射外源性尿激酶型纖溶酶原激活物引起雙側(cè)膝關(guān)節(jié)軟骨降解的實驗[J];中國組織工程研究與臨床康復(fù);2007年19期

10 高石軍,陳百成,湯慧華,樊錫風(fēng),孫建海,馮忠軍,任啟富,郭曉華;一氧化氮在骨性關(guān)節(jié)炎發(fā)病機制中的作用[J];中華骨科雜志;1999年07期

，

本文編號：1454255