来源：风湿病与关节炎,2019,8（11）:5-10.

塞来昔布对骨关节炎大鼠软骨组织AQP1和AQP3表达影响的研究（基础研究）

郑世雄，刘合亮，杨　巍，魏艳珍，林亮明

　　【摘　要】目的：研究塞来昔布对骨关节炎模型大鼠软骨组织水通道蛋白1（AQP1）和水通道蛋白3（AQP3）分布与表达的影响。方法：将45只SD大鼠随机分为空白对照组、模型对照组、塞来昔布组，每组15只。模型对照组和塞来昔布组采用关节腔注射木瓜蛋白酶建立模型。塞来昔布组采用17.85 mg·kg^-1·d^-1塞来昔布灌胃，另外2组采用等量生理盐水灌胃。取左侧膝关节HE染色、甲苯胺蓝染色观察软骨组织形态，免疫组化观察AQP1、AQP3表达，ELISA检测血清白细胞介素-1β（IL-1β）含量；取右侧膝关节Real-time PCR、Western Blot检测软骨组织AQP1、AQP3表达。结果：与空白对照组比较，模型对照组软骨面缺损，细胞排列紊乱，甲苯胺蓝染色重度减弱，Mankin评分显著升高（P < 0.01），移行层AQP1、AQP3表达显著升高（P < 0.05或P < 0.01），血清IL-1β表达升高（P < 0.01），AQP1、AQP3 mRNA和蛋白表达均升高（P < 0.05）。与模型对照组比较，塞来昔布组软骨面缺损较小，细胞排列较规则，甲苯胺蓝染色较深，Mankin评分降低（P < 0.05），移行层AQP3表达降低（P < 0.05），血清IL-1β表达降低（P < 0.01），AQP3 mRNA和蛋白表达降低（P < 0.01）。结论：塞来昔布可降低AQP3的分布范围和表达量，降低软骨组织渗透性，可能是其治疗骨关节炎的潜在作用机制之一。

　　【关键词】　骨关节炎；塞来昔布；水通道蛋白1；水通道蛋白3；大鼠

Effects of Celecoxib on the Expressions of AQP1 and AQP3 in the Cartilage of Rats with  Osteoarthritis

ZHENG Shi-xiong,LIU He-liang,YANG Wei,WEI Yan-zhen,LIN Liang-ming

　　【ABSTRACT】Objective:To study the effects of celecoxib on the distribution and expressions of AQP1 and AQP3 in the cartilage of rats with osteoarthritis.Methods:Forty-five SD rats were randomly divided into a blank control group,a model control group and a celecoxib group,with 15 rats in each.In the model control group and the celecoxib group,papain was injected into the articular cavity to establish models.In the celecoxib group,17.85 mg·kg^-1·d^-1 of celecoxib was administered to the stomach,and in the other two groups,the same amount of normal saline was administered to the stomach.HE staining and toluidine blue staining were used to observe the cartilage morphology of the left knee joint,the expressions of AQP1 and AQP3 was observed by immunohistochemistry,and the content of IL-1β in serum was detected by ELISA.The expressions of AQP1 and AQP3 in cartilage of the right knee joint were detected by real-time PCR and Western blot.Results:Compared with the blank control group,the model control group had cartilage defects,disordered cell arrangement,weakened toluidine blue staining,significantly increased Mankin score（P < 0.01）,significantly increased AQP1 and AQP3 expressions in the transitional layer（P < 0.05 or P < 0.01）,increased IL-1β expression in serum（P < 0.01）,and increased AQP1,AQP3 mRNA and protein expressions（P < 0.05）.Compared with the model control group,the defect of cartilage surface in the celecoxib group was smaller,the cell arrangement was more regular,toluidine blue staining was deeper,Mankin score was lower（P < 0.05）,AQP3 expression in the transitional layer was lower（P < 0.05）,IL-1β expression in serum was lower（P < 0.01）,and AQP3 mRNA and protein expressions were lower（P < 0.01）.Conclusion:Celecoxib can reduce the distribution and expression of AQP3 and the permeability of cartilage tissue,which may be one of the potential mechanisms of treating osteoarthritis.

　　【Keywords】 osteoarthritis;celecoxib;aquaporin 1;aquaporin 3;rats