Effect of leflunomide regulating HIF-1α signal pathway on autophagy of synoviocytes in rheumatoid arthritis
10.19405/j.cnki.issn1000-1492.2024.10.018
- VernacularTitle:来氟米特调控HIF-1α信号通路对类风湿关节炎滑膜细胞自噬的影响
- Author:
Weiya LAN
1
;
Wukai MA
;
Xueming YAO
;
Zong JIANG
;
Lang XIONG
;
Shufen YANG
;
Fang TANG
Author Information
1. 贵州中医药大学第二临床医学院,贵阳 550025
- Keywords:
rheumatoid arthritis;
leflunomide;
HIF-1α signal pathway;
autophagy;
synovitis
- From:
Acta Universitatis Medicinalis Anhui
2024;59(10):1823-1828
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of leflunomide(LEF)on the expression of associated autophagy genes in synoviocytes of rheumatoid arthritis(RA)by regulating HIF-1α signal pathway.Methods Three genera-tions of RA synovial cells were divided into blank control group,LEF group and Tripterygium wilfordii polyglyco-sides group.The blank control group was added with the same volume of DMEM culture medium.The drug group was treated with LEF(concentration 0.2 mg/ml)and Tripterygium wilfordii polyglycosides(concentration 0.03 mg/ml),the proliferation and apoptosis of synovial cells were detected by flow cytometry,the expression of IL-1 β,TNF-α,ANGPTL-4 and VEGF was detected by ELISA,the expression of HIF-1α mRNA was detected by qRT-PCR,and the expression of HIF-1 α,Beclin-1 and BNIP3 protein was detected by Western blot.Results Com-pared with Tripterygium wilfordii polyglycosides group,the expression of IL-1 α,TNF-α,ANGPTL-4 and VEGF in synovial supernatant of LEF group decreased;compared with the blank control group,the expression of HIF-1αmRNA in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious;compared with the blank control group,the protein expressions of HIF-1α,Bec-lin-1 and BNIP3 in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious.Conclusion LEF can inhibit the expression of inflammatory factors in RA synovial cells,inhibit HIF-1α signaling pathway,inhibit the expression of autophagy-related genes Beclin-1 and BNIP3,and improve the pathological state of synovitis.
