臭氧通过调节HIF-1α-VEGF信号通路治疗类风湿关节炎的实验研究  

Protective effects of ozone on rheumatoid arthritis in rats by regulating HIF-1α-VEGF signaling pathway

作　　者：杨妮娜 詹景棣 柳海晓[2] 许心弦[2] YANG Nina;ZHAN Jingdi;LIU Haixiao(Department of Critical Care Medicine,the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第二医院(育英儿童医院)急诊重症监护室科,325000 [2]温州医科大学附属第二医院(育英儿童医院)关节外科,325000

出　　处：《浙江医学》2019年第21期2265-2268,2273,共5页Zhejiang Medical Journal

基　　金：温州市公益性科技计划项目(Y20170236)

摘　　要：目的探索臭氧通过调节低氧诱导因子-1α(HIF-1α)-血管内皮生长因子(VEGF)通路对类风湿关节炎(RA)的治疗机制。方法将30只Wistar大鼠随机分为对照组(Con组)、类风湿关节炎组(RA组)、O3治疗组(O3组),采用弗氏完全佐剂乳化的牛Ⅱ型胶原诱导建立RA大鼠模型。O3组大鼠右膝关节腔注射O3,Con组和RA组局部注射0.9%氯化钠溶液,治疗结束后测量各组大鼠膝关节肿胀率,并检测各组血清、关节液及滑膜组织HIF-1α和VEGF蛋白表达水平,及滑膜组织HIF-1α和VEGF mRNA表达水平。结果与Con组比较,RA组和O3组大鼠膝关节肿胀率明显增高,血清、关节液及滑膜组织HIF-1α和VEGF蛋白表达明显升高(P<0.05),滑膜组织HIF-1α和VEGF mRNA表达水平也显著升高(P<0.05)。与RA组比较,O3组右膝关节肿胀率明显减小(P<0.05),关节液及滑膜组织中表达水平明显下降(P<0.05),滑膜组织上述因子mRNA表达水平也显著下降(P<0.05),但血清中上述细胞因子表达水平无统计学差异(P>0.05)。结论臭氧可以通过抑制关节内HIF-1α、VEGF的表达水平,调控HIF-1α-VEGF信号通路来治疗类风湿关节炎。Objective To investigate the effect of ozone(O3) on rheumatoid arthritis(RA) and its mechanism in rats by regulating hypoxia-induciblefactor-1α(HIF-1α)-vascularendothelialgrowthfactor(VEGF) signaling pathway. Methods Thirty Wistar rats were randomly allocated into control group, RA group and O3 group. The RA was induced by hypodermic injection of collagen Ⅱ with complete Feund’s adjuvant. Rats in O3 group were injected with O3 in the right knee, and those in control group and RA group were injected with normal saline. At the end of treatment, the swelling rate of the knee was evaluated;the protein levels of HIF-1α and VEGF in serum, synovia and synovial tissue as well as their mRNA levels in synovial tissue were detected.Results Compared with Control group, the swelling rate of the knee, the protein levels of HIF-1α and VEGF in serum, synovia and synovial tissue and their mRNA levels in synovial tissue were significantly higher in RA group(P<0.05). Compared with RA group, the swelling rate of the knee, the protein levels of HIF-1α and VEGF in synovia and synovial tissue and the mRNA levels in synovial tissue were significantly reduced in O3 group(P<0.05), while the protein levels of HIF-1α and VEGF in serum showed no significant difference between RA group and O3 group(P >0.05). Conclusion Ozone can inhibit the local expression levels of HIF-1α and VEGF by regulating the HIF-1α-VEGF signaling pathway in RA rats, thus attenuating the progress of RA.

关 键 词：臭氧 类风湿关节炎 HIF-1Α VEGF 

分 类 号：R73[医药卫生—肿瘤]