MiR-146a介导依那西普对强直性脊柱炎活动期患者炎症因子和骨代谢的影响  

The Effect of MiR-146a Mediated Etanercept on the Inflammatory Factors and Bone Metabolism in Patients with Ankylosing Spondylitis

作　　者：直彦亮[1] 林思薪 贺宪[1] 张震 ZHI Yan-liang;LIN Si-xin;HE Xian;ZHANG Zhen(Panyu Hospital of Chinese Medicine,Guangzhou Guangdong,511400;Shenzhen Hospital of Integrated Chinese and Western Medicine,Shenzhen Guangdong,518104)

机构地区：[1]广州市番禺区中医院,广东广州511400 [2]深圳市中西医结合医院,广东深圳518104

出　　处：《山西大同大学学报（自然科学版）》2021年第3期64-67,共4页Journal of Shanxi Datong University(Natural Science Edition)

基　　金：国家自然科学基金[81574000]。

摘　　要：目的探讨依那西普对强直性脊柱炎(AS)活动期患者miR-146a表达的影响以及miR-146a影响炎症因子和骨代谢的可能机制方法将强直性脊柱炎活动期患者分为依那西普组和柳氮磺吡啶组,治疗3月后进行RT-qPCR检测。将BALB/c小鼠分为强直性脊柱炎组(模型对照组)、依那西普组、miR-146a抑制剂组、依那西普+miR-146a抑制剂组,以及miR-146a抑制剂阴性对照组共5组,治疗4周后,检测小鼠血清C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)、白介素6(IL-6)、甲状旁腺素(PTH)、骨保护素(OPG)、骨碱性磷酸酶(BALP)和骨钙素(OC)水平,Westernblot检测Wnt/β-catenin通路蛋白、OPG/细胞核因子KB受体活化因子配体(RANKL)/细胞核因子KB受体活化因子(RANK)通路蛋白。结果依那西普可以抑制AS活动期患者miR-146a的表达;miR-146a抑制剂可以模拟依那西普作用,明显降低小鼠血清CRP、TNF-α、IL-6、BALP水平,提高血清PTH、OPG、BALP和OC水平;显著上调小鼠脊柱组织中Wnt、β-catenin、OPG蛋白表达,而显著下调RANKL、RANK表达,差异具有显著性意义。两者合用后效果更好。结论依那西普可能通过抑制miR-146a表达调节成骨和破骨过程,从而表现出改善炎症反应和骨代谢作用。Objective To explore the effect of Etanercept on the expression of miR-146a in patients with active ankylosing spon-dylitis(AS)and the possible mechanism of miR-146a on inflammatory factors and bone metabolism.Method Patients with active AS were divided into two groups:Etanercept group and SASP group;BALB/c mice were divided into five groups:AS group(model control group),Etanercept group,miR-146a inhibitor group,Etanercept+miR-146a inhibitor group,and negative control group(Negative Con).After treatment for four weeks,the levels of serum C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),inter-leukin6(IL-6),parathyroid hormone(PTH),osteoprotegerin(OPG),bone alkaline phosphatase(BALP)and Osteocalcin(OC)were measured.The protein level of Wnt/β-Catenin patheway was observed by Western blot assay,and OPG/nuclear factor B receptor ac-tivating factor ligand(RANKL)/nuclear factor B receptor activating factor(RANK)pathway.Results Etanercept could inhibit the expression of miR-146a in patients with AS;MiR-146a inhibitor could mimic the effect of Etanercept,which decreased the levels of CRP,TNF-α,IL-6 and BALP,and increased the levels of PTH,OPG,and OC in serum of BALB/c mice;Meanwhile miR-146a up regulated the expression of Wnt,β-Catenin and OPG but down-regulated the expression of RANKL and RANK significantly as well as Etanercept;There were significant differences between Etanercept group,miR-146a inhibitor group and Negative Con.The effect was better when they were combined.Conclusion Enalapril may modulate the osteogenesis and osteoclastic process by inhibiting the expression of miR-146a,so as to improve the inflammation and bone metabolism.

关 键 词：依那西普 MIR-146A 炎症因子 骨代谢 

分 类 号：R593.23[医药卫生—内科学]