关节腔内注射强力霉素对兔制动骨关节炎模型膝关节退变的影响

发布时间：2018-01-22 08:45

本文关键词： 骨关节炎强力霉素 IL-1 uPA MMPs-3 NO NOS　出处：《石河子大学》2010年硕士论文　论文类型：学位论文

【摘要】：目的:研究关节腔内注射强力霉素对制动兔骨关节炎模型膝关节退变的影响,探讨其作用机制。方法：48只新西兰大白兔随机分成止常组6只及实验组42只,试验组左膝关节伸直位石膏固定4周随机选取6只(石膏固定4周组)处死左膝关节取材证实造模成功后剩余36只拆除石膏制成骨关节炎模型,随机分为治疗组、阴性对照组和模型对照组,治疗组每日给予1.33%的强力霉素0.3毫升左膝关节腔内注射,阴性对照组每日给予生理盐水0.3毫升左膝关节腔注射,模型对照组不做处理,于4周及8周处死取材。观察指标包括关节软骨大体形态,软骨Mankin's评分,关节液一氧化氮(NO)及一氧化氮合酶(NOS)活性,软骨细胞基质金属蛋白酶-3(MMP-3)、尿激酶型纤溶酶原激活物(uPA)表达及滑膜细胞白介素-1(IL-1)表达。结果：(1)与正常对照组比较,石膏固定4周组软骨表面有溃疡形成,Mankin's评分明显高于正常对照组,软骨uPA、MMPs-3活性及滑膜IL-1活性均较高,关节液NO含量及NOS活性也高与正常对照组(P0.05)；(2)与石膏固定4周组比较,4周模型对照组,Mankin's评分明显增高(P0.05),软骨uPA、MMPs-3活性、滑膜IL-1活性及关节液NO含量及NOS活性较高(P0.05),8周时增加更加明显(P0.05)；(3)与4周模型对照组比较,4周阴性对照组,Mankin's评分明显增高(P0.05),软骨uPA、MMPs-3活性、滑膜IL-1活性及关节液NO含量及NOS活性较高(P0.05),8周则无明显差异(P0.05)；(4)与模型对照组及阴性对照组比较,治疗组软骨面光滑,Mankin's评分较低(P0.05),软骨uPA、MMPs-3舌性、滑膜IL-1活性及关节液NO含量及NOS活性均降低(P0.05),但仍高丁正常对照组。结论：1、伸直位石膏固定4周可获得满意的骨关节炎模型,关节退变随病程进展而进展；2、强力霉素关节腔内注射给药,可对兔膝骨关节炎软骨退变起明显缓解作用,其作用机制与软骨中uPA、MMP-13及滑膜中IL-1表达的抑制,抑制NO的产生及NOS活性等作用有关。
[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.
【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R684.3;R-332

【参考文献】