来源：风湿病与关节炎,2021,10（12）:1-6.

氟尿嘧啶对膝骨关节炎模型大鼠膝关节软骨、滑膜损伤的影响（临床研究）

肖莉莉，林　煜，郑世雄，林丽琼，冯尔宥，王武炼

　　【摘　要】通过观察氟尿嘧啶对膝骨关节炎大鼠软骨基质成分的影响，探讨其对早期膝骨关节炎的疗效。方法：采用改良Hulth法切除前交叉韧带、切断和切除内侧半月板造模，空白对照组仅切开后缝合，模型对照组和氟尿嘧啶组均按上述方法造模，每组12只。术后6周，空白对照组和模型对照组在膝关节腔内注射生理盐水对照，氟尿嘧啶组膝关节腔内注射重组氟尿嘧啶注射液2 mg·kg^-1。HE染色在光学显微镜下观察关节软骨组织变化，甲苯胺蓝软骨基质染色后按照Mankin评分标准进行病理评分，采用免疫组织化学染色对膝关节软骨骨桥蛋白的表达进行半定量分析，并用ELISA试剂盒检测滑膜组织钙结合蛋白S100A12、、白细胞介素-1β（IL-1β）和半乳糖凝集素3（galectin-3）的表达。结果：氟尿嘧啶组大鼠膝骨关节炎模型滑膜中钙结合蛋白S100A12、NO、IL-1β、galectin-3含量较模型对照组明显减少，软骨中骨桥蛋白的表达也较模型对照组减少，差异有统计学意义（P < 0.05）；同时关节滑膜的炎症反应也明显减轻。结论：通过关节腔注射氟尿嘧啶治疗大鼠膝骨关节炎模型，能够改善病变关节内的微环境，抑制滑膜炎症，减少关节滑液中致炎因子，从而延缓关节软骨退变，有较好的治疗作用。

　　【关键词】　膝骨关节炎；氟尿嘧啶；软骨基质成分；形态学；大鼠

Effect of Fluorouracil on Injury of Knee Cartilage and Synovium in Rat Models with Knee Osteoarthritis  

XIAO Li-li,LIN Yu,ZHENG Shi-xiong,LIN Li-qiong,FENG Er-you,WANG Wu-lian

　　【ABSTRACT】Objective:By investigating the effect of fluorouracil on the composition of cartilage matrix in rats with knee osteoarthritis to explore its curative effect on early knee osteoarthritis.Methods:The modified Hulth method was used to cut the anterior cruciate ligament and cut off the medial meniscus.Those in the blank control group were only cut and sutured.The model control group and the fluorouracil group were modeled according to the above methods,with 12 rats in each group.Six weeks after operation,normal saline was injected into the knee joint of the blank control group and the model control group,and recombinant fluorouracil injection（2 mg·kg^-1）was injected into the knee joint of the fluorouracil group.HE staining was used to observe the changes of articular cartilage under the light microscope.Toluidine blue cartilage matrix staining was followed by pathological scoring according to the Mankin scoring standard.The expression of osteopontin in knee cartilage was semi-quantitatively analyzed by immunohistochemical staining,and the calcium binding protein S100A12,nitric oxide（NO）,interleukin-1β（IL-1β）and galectin-3 in synovial tissue were detected by ELISA kit.Results:The contents of calcium binding protein S100A12,NO,IL-1β and galectin-3 in synovium of the fluorouracil group were significantly lower than those in the model control group,and the expression of osteopontin in cartilage was also lower than that in the model control group,the difference being statistically significant（P < 0.05）;At the same time,the inflammatory reaction of joint synovium was also significantly reduced.Conclusion:Intra articular injection of fluorouracil in the treatment of rat knee osteoarthritis model can improve the microenvironment in the diseased joint,inhibit synovial inflammation,reduce inflammatory factors in joint synovial fluid,so as to delay the degeneration of articular cartilage.

　　【Keywords】 knee osteoarthritis;fluorouracil;cartilage matrixomponents;morphology;rats