[1]王颖,韦颖梅,程秀,等.2-脱氧葡萄糖通过激活AMPK通路抑制类风湿关节炎血管新生[J].南方医科大学学报,2018,(08):962.
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2-脱氧葡萄糖通过激活AMPK通路抑制类风湿关节炎血管新生()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2018年08期
页码:
962
栏目:
出版日期:
2018-07-31

文章信息/Info

Title:
2-deoxyglucose inhibits angiogenesis of rheumatoid arthritis via activating AMPK pathway
作者:
王颖韦颖梅程秀孙小锦马琳艳宋宜宁周静魏芳刘浩
关键词:
类风湿关节炎血管新生2-脱氧葡萄糖糖酵解AMPK通路
Keywords:
rheumatoid arthritis angiogenesis 2-deoxyglucose glycolysis AMPK pathway
摘要:
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。
Abstract:
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). Conclusion 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.

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更新日期/Last Update: 1900-01-01