目的 探討木瓜蛋白酶誘導(dǎo)兔膝關(guān)節(jié)骨關(guān)節(jié)炎模型的滑膜病理變化。方法 納入30只新西蘭大白兔，隨機(jī)分為對(duì)照和模型組，模型組動(dòng)物均采用木瓜蛋白酶注射方式制備膝關(guān)節(jié)骨關(guān)節(jié)炎模型，術(shù)后2、4、6周，分別取兩組各5只動(dòng)物，處死后獲得滑膜組織標(biāo)本，觀察一般情況，對(duì)兩組不同時(shí)間的滑膜進(jìn)行Mankin評(píng)分；蘇木精-伊紅（HE）染色觀察病理變化；酶聯(lián)免疫法檢測(cè)滑膜血管內(nèi)皮生長(zhǎng)因子（VEGF）和白細(xì)胞介素-1β（IL-1β）表達(dá)水平。結(jié)果 木瓜蛋白酶單次注射后第2周，對(duì)模型組動(dòng)物進(jìn)行病理觀察，可見膝關(guān)節(jié)出現(xiàn)嚴(yán)重的滑膜炎性反應(yīng)，滑膜細(xì)胞與下層疏松纖維及血管組織均明顯增生，并存在大量淋巴漿細(xì)胞浸潤(rùn)；隨著時(shí)間推移，炎性反應(yīng)逐漸減輕。隨著注射時(shí)間的延長(zhǎng)，模型組Mankin評(píng)分、VEGF和IL-1β表達(dá)水平均呈下降趨勢(shì)，對(duì)照組無(wú)明顯變化；模型組木瓜蛋白酶注射后2、4周的Mankin評(píng)分、VEGF和IL-1β表達(dá)水平均顯著高于對(duì)照組（P < 0.05），注射后6周的Mankin評(píng)分、VEGF和IL-1β表達(dá)水平與對(duì)照組化比較差異無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論 木瓜蛋白酶可以誘導(dǎo)兔膝關(guān)節(jié)骨關(guān)節(jié)炎模型，木瓜蛋白酶單次注射后第2周，兔膝關(guān)節(jié)滑膜炎性反應(yīng)嚴(yán)重，第4、6周時(shí)炎性反應(yīng)逐漸減輕。

Objective To investigate the effect of papain on pathological changes of synovial membrane in knee osteoarthritis rabbit model. Method Totally 30 New Zealand white rabbits were randomly divided into control group and model group with 15 rabbits in each group. Two groups of five animals were sacrificed to, obtain membrane tissue for observation in two, four and six weeks after operation. Two groups of synovium were evaluated by Mankin score at different time. Hematoxylin eosin (HE) staining was used to observe pathological changes. The expression level of vascular endothelial growth factor (VEGF) and interleukin-1 beta (IL-1β) in synovial membrane were detected by ELISA. Results Papain once injection after two weeks, the animals of model group were observed. The visible knee appeared serious inflammatory reaction, synovial cells, lower loose fibrous tissue, and blood vessels were significantly hyperplasia, and there was a large amount of lymphoplasmacytic infiltration. As time goes on, the inflammatory response was gradually reduced. With the extension of injection time, Mankin score, VEGF and IL-1β expression levels of model group showed a declining trend, but no apparent change in the control group. Mankin score, VEGF and IL-1β expression levels of model group after two and four weeks papain injection were significantly higher than those in control group (P < 0.05). Six weeks after the injection, Mankin score, VEGF and IL-1β expression levels had no significant difference compared with control group. Conclusion Papain can induce knee osteoarthritis in rabbit models. Two weeks after a single injection of papain, the inflammatory reaction of knee joint synovitis is serious in rabbits, and the inflammatory reaction is gradually alleviated after four and six weeks.