Taxol alleviates collagen-induced arthritis in mice by inhibiting the formation of microvessels.
Taxol alleviates collagen-induced arthritis in mice by inhibiting the formation of microvessels.
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DOI：
10.1007/s10067-017-3646-1
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发表时间：
2019-01
影响因子：
3.4
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Xu J;Feng Z;Chen S;Zhu J;Wu X;Chen X;Li J
本研究的目的是评价紫杉醇（PTX）对胶原诱导的关节炎（CIA）小鼠模型血管生成的抑制作用。在C57 BL/6（H-2b）小鼠中使用胶原II（C II）和完全弗氏佐剂（CFA）以产生CIA模型。随机分为正常对照组、CIA模型组、PTX 1.5 mg/kg组、PTX 1.0 mg/kg组、PTX 0.5 mg/kg组。进行关节炎指数评分、组织病理学评分和滑膜微血管密度（MVD）分析。采用免疫组化和酶联免疫吸附法检测血管内皮生长因子（VEGF）和缺氧诱导因子-α（HIF-1α）的表达。分析滑膜组织中VEGF、HIF-1α的表达与MVD及病理评分的相关性。PTX治疗后，与CIA组相比，三个干预组的关节炎指数评分均降低。三个PTX治疗组的总组织学评分均低于CIA组。同样，PTX显著减轻了滑膜炎、血管翳形成和骨破坏的评分。与CIA组相比，3个干预组的MVD呈剂量依赖性下降。PTX治疗后滑膜组织和血清中VEGF和HIF-1α的表达也明显降低。进一步分析发现，滑膜组织中MVD与病理评分、VEGF和HIF-1α的表达呈正相关。PTX可能通过抑制血管生成来缓解CIA，为类风湿性关节炎（RA）的治疗提供了新的见解。VEGF和HIF-1α可能是PTX抑制微血管形成的靶点。
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 1.5 mg/kg group, PTX 1.0 mg/kg group, and PTX 0.5 mg/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-α (HIF-1α). The correlation between MVD and pathological scores and between MVD and the expression of VEGF as well as HIF-1α 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-1α 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-1α 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-1α may be targets for PTX suppression of microvessel formation.
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DOI：
10.1186/1476-9255-6-10
发表时间：
2009-04-15
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Liang B;Song Z;Wu B;Gardner D;Shealy D;Song XY;Wooley PH
通讯作者：
Wooley PH
影响因子：
8.6
作者：
Clavel, Gaeelle;Bessis, Natacha;Boissier, Marie-Christophe
通讯作者：
Boissier, Marie-Christophe
影响因子：
11.2
作者：
Escuin, D;Kline, ER;Giannakakou, P
通讯作者：
Giannakakou, P
影响因子：
5.6
作者：
Birukova, AA;Smurova, K;Verin, AD
通讯作者：
Verin, AD
影响因子：
--
作者：
BRAHN, E;TANG, C;BANQUERIGO, ML
通讯作者：
BANQUERIGO, ML