Objective: To observe the effects of 2-deoxyglucose inhibiting synovial pannus of adjuvant arthritis rats and to explore its potential mechanism of inhibiting angiogenesis by investigating proliferation, migration and matrigel tube formation assay in vitro.
Methods: The effect of 2-DG on synovial pannus was evaluated by histopathology of HE staining; HUVEC proliferation was determined by CCK-8 method; migration of FLS were determined by transwell; In vitro matrigel tube formation assay was made for assessing tube number of HUVEC; p-AMPK and Bcl-2 were detected by Western blot assay; AMPK signaling pathway in HUVEC was inhibited by compound C, which is an inhibitor of AMPK activation.
Results: 2-DG (200 mg/kg) obviously decreased appearance of synovial pannus (P < 0.01); in vitro, 2-DG (0.5 mmol/L and/or 5 mmol/L) obviously inhibited proliferation, migration and tube number of HUVEC (P < 0.01 or P < 0.001), and its effects on HUVEC were reversed by using AMPK antagonist (Compound C); Western blot showed that 2-DG (5 mmol/L) increased expression of p-AMPK and decreased expression of Bcl-2 (P < 0.05).
Conclusions: Activating AMPK pathway and decreasing expression of Bcl-2 may the potential mechanism by which 2-DG contributes to anti-angiogenesis and effects of inhibiting proliferation, migration and tube number of HUVEC.
目的: 通过观察2-脱氧葡萄糖（2-DG）对佐剂关节炎（AA）大鼠滑膜组织血管翳形成的抑制及对人脐静脉内皮细胞（HUVEC）增殖、迁移和体外成管的作用，探讨2-DG抑制类风湿关节炎血管新生的机制。
方法: 采用滑膜病理组织HE染色观察滑膜组织血管翳形成；CCK-8法检测HUVEC的细胞增殖活性；Transwell小室法检测HUVEC的迁移；体外基质胶成管实验检测HUVEC的成管数；Western blot检测p-AMPK以及抗凋亡蛋白Bcl-2的表达；使用AMPK阻断剂Compound C阻断HUVEC细胞的AMPK信号通路。
结果: 2-DG（200 mg/kg）明显减轻AA大鼠滑膜组织血管翳生成（P < 0.01）；体外实验结果显示，2-DG（0.5 mmol/L和/或5 mmol/L）可明显抑制HUVEC的增殖、迁移和体外成管（P < 0.01或P < 0.001），加入AMPK受体阻断剂Compound C（5 μmol/L），2-DG对HUVEC的活化的抑制作用被明显阻断（P < 0.01）；Western blot结果显示2-DG（5 mmol/L）可以增加P-AMPK的蛋白表达，减少Bcl-2的蛋白表达，差异有统计学意义（P < 0.05）。
结论: 2-DG可能通过激活AMPK通路减少Bcl-2的表达抑制内皮细胞增殖、迁移和体外成管，从而抑制类风湿关节炎血管新生。
Keywords: 2-deoxyglucose; AMPK pathway; angiogenesis; glycolysis; rheumatoid arthritis.