Taxol alleviates collagen-induced arthritis in mice by inhibiting the formation of microvessels

被引:26
作者
Xu, Juan [1 ]
Feng, Zhitao [1 ,2 ]
Chen, Shixian [1 ]
Zhu, Junqing [3 ]
Wu, Xianghui [4 ]
Chen, Xiaoguang [5 ]
Li, Juan [1 ,3 ]
机构
[1] Southern Med Univ, Coll Tradit Chinese Med, Dept Internal Med Tradit Chinese Med, Guangzhou 510515, Guangdong, Peoples R China
[2] China Three Gorges Univ, Coll Med, Dept Tradit Chinese Med, Yichang 443002, Hubei, Peoples R China
[3] Southern Med Univ, Nanfang Hosp, Dept Rheumatol, 1838 North Guangzhou Ave, Guangzhou 510515, Guangdong, Peoples R China
[4] Southern Med Univ, Nanfang Hosp, Lab Anim Ctr, Guangzhou 510515, Guangdong, Peoples R China
[5] Southern Med Univ, Sch Publ Hlth, Dept Pathogen Biol, Guangzhou 510515, Guangdong, Peoples R China
基金
美国国家科学基金会;
关键词
Angiogenesis; Hypoxia-inducible factor-1; Rheumatoid arthritis; Taxol; Vascular endothelial growth factor; PACLITAXEL AMELIORATES FIBROSIS; RHEUMATOID-ARTHRITIS; INDUCED INFLAMMATION; ANGIOGENESIS; CELLS; RECEPTOR; HYPOXIA; VEGF; MICROTUBULES; CHECKPOINT;
D O I
10.1007/s10067-017-3646-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The objective of the present study is to evaluate the inhibitory effects of taxol (PTX) on angiogenesis in a collagen-induced arthritis (CIA) mouse model. Collagen II (C II) and complete Freund's adjuvant (CFA) were used in C57BL/6 (H-2b) mice to generate the CIA model. Random grouping was performed in the normal control group, CIA model group, PTX 1.5mg/kg group, PTX 1.0mg/kg group, and PTX 0.5mg/kg group. Arthritis index scores, tissue pathology scores, and synovium microvessel density (MVD) analysis were performed. Immunohistochemistry and enzyme-linked immunosorbent assay were used to detect the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor- (HIF-1). The correlation between MVD and pathological scores and between MVD and the expression of VEGF as well as HIF-1 in the synovium were also evaluated. After PTX treatment, the three intervention group arthritis index scores were reduced when compared with the CIA group. The total histological scores in the three PTX treatment groups were lower than those in the CIA group. Similarly, PTX significantly alleviated the scores for synovitis, pannus formation, and bone destruction. Compared with the CIA group, the MVD of the three intervention groups decreased in a dose-dependent manner. The expression of VEGF and HIF-1 in synovial tissues and serum also significantly decreased after PTX treatment. Further analysis showed that MVD and pathological scores and MVD and expression of VEGF as well as HIF-1 in the synovium were positively correlated. PTX may alleviate CIA by suppressing angiogenesis, providing new insights into the treatment of rheumatoid arthritis (RA). VEGF and HIF-1 may be targets for PTX suppression of microvessel formation.
引用
收藏
页码:19 / 27
页数:9
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