Sinomenine mitigates collagen-induced arthritis mice by inhibiting angiogenesis
Sinomenine mitigates collagen-induced arthritis mice by inhibiting angiogenesis
复制标题
青藤碱通过抑制血管生成减轻胶原诱导的关节炎小鼠
DOI：
10.1016/j.biopha.2019.108759
复制
发表时间：
2019-05-01
影响因子：
7.5
通讯作者：
Mei, Zhi-gang
中科院分区：
文献类型：
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作者：
Feng, Zhi-tao;Yang, Tong;Mei, Zhi-gang
目的：本研究的目的是探讨青藤碱（SIN）对胶原诱导关节炎（CIA）小鼠模型血管生成的抑制作用。在苏木精和伊红（HE）染色后进行组织病理学评估。采用免疫组化和酶联免疫吸附试验（ELISA）检测血清和细胞膜中缺氧诱导因子-1 α（HIF-1 alpha）、血管内皮生长因子（VEGF）和血管生成素1（ANG-1）的表达。结果：与CIA模型组相比，SIN能明显改善CIA大鼠关节肿胀、红斑范围，降低关节炎指数，减轻炎症反应、软骨损伤和骨质侵蚀，减少滑膜表面CD 31阳性细胞数量。结论：SIN通过抑制血管生成减轻CIA，其机制可能与HIF-1 α-VEGF-ANG-1轴有关。本研究为SIN治疗类风湿关节炎提供了可靠的实验依据。
Objective: The objective of the present study is to investigate the inhibitory effects of sinomenine (SIN) on angiogenesis in a collagen-induced arthritis (CIA) mouse model.Methods: Arthritis assessments for all mice were recorded. The histopathological assessments were performed following haematoxylin and eosin (HE) staining. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) analyses were used to detect the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF) and angiopoietin 1 (ANG-1) in the serum and in the membrane. Immunohistochemistry was employed to detect the synovium microvessel density (MVD).Results: Compared with the CIA model group, SIN significantly ameliorated swelling and erythema extension, decreased the arthritis index, reduced inflammation, cartilage damage and bone erosion, and lessened the number of CD31 positive cells on the synovium. Moreover, the levels of HIF-1 alpha, VEGF and ANG-1 in the synovium and in the peripheral serum were increased in the untreated CIA model group but were significantly reduced in the 30 mg/kg, 100 mg/kg and 300 mg/kg SIN treatment groups.Conclusion: SIN could mitigate CIA by inhibiting angiogenesis, and the mechanism may associate with the HIF-1 alpha-VEGF-ANG-1 axis. Additionally, our study provides a referable experimental basis for the use of SIN for the treatment of rheumatoid arthritis.