MiR-145-5p对胶原诱导的关节炎小鼠关节炎症的影响

Effects of miR-145-5p on joint inflammation in collagen-induced arthritis mice

目的:探讨miR-145-5p对胶原诱导的关节炎(CIA)小鼠关节变化的影响。方法:采用牛Ⅱ型胶原免疫DBA/1小鼠诱导CIA,对关节指数评分及足跖肿胀程度进行比较,成模后随机分为agomiR-145-5p组和agomiR空载体(agomiR-NC)组进行干扰,采用足爪micro-CT摄片,踝关节病理检查评分及石蜡切片、HE染色进行处理,并通过免疫组化方法(IHC)检测踝关节中金属蛋白酶-1(MMP-1)、金属蛋白酶-3(MMP-3)、金属蛋白酶-9(MMP-9)、金属蛋白酶-13(MMP-13)、白细胞介素17(IL-17)和金属蛋白酶17(ADAM17)的表达。结果:成功建立CIA小鼠模型,与agomiR-NC组相比,agomiR-145-5p组micro-CT分析显示骨侵蚀更严重,组织病理学显示滑膜炎症减轻,免疫组化结果显示MMP-3、MMP-9、MMP-13和IL-17水平升高,MMP-1水平无差异,ADAM17水平降低(P<0.05)。结论:成功建立CIA小鼠模型,并发现mi R-145-5p加重关节破坏的同时部分抑制了CIA小鼠的关节炎症。

Objective: To investigate the effect of miR-145-5p on joint changes in collagen-induced arthritis (CIA) mice. Methods:The CIA was induced by immunization of bovine type II collagen in DBA/1 mice, and the joint index scores and degree of paw swelling were compared. After the model was formed, they were randomly divided into agomiR-145-5p group and agomiR-NC group toperform interference.Foot micro-CT radiographs, ankle pathology score, paraffin sections, and HE staining were measured. IHC was used to detect the expression of MMP-1, MMP-3, MMP-9, MMP-13, IL-17 and ADAM17 in the ankle joint. Results:The CIA mouse model was successfully established. Compared with the agomiR-NC group, bone erosion was more severe in the agomiR-145-5p group. Histopathology showed synovial inflammation was reduced, and immunohistochemistry showed MMP-3 and MMP-9, MMP-13 and IL-17 levels increased, MMP-1 levels were not different, and ADAM17 levels decreased (P<0.05). Conclusion: We have successfully established a CIA mouse model and found that miR-145-5p could aggravate joint destruction while partially inhibiting joint inflammation in CIA mice.