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紫杉醇对胶原诱导性关节炎的消退作用:与滑膜炎和新生血管形成抑制的超微结构相关性

Taxol involution of collagen-induced arthritis: ultrastructural correlation with the inhibition of synovitis and neovascularization.

作者信息

Arsenault A L, Lhoták S, Hunter W L, Banquerigo M L, Brahn E

机构信息

Department of Pathology, McMaster University, Hamilton, Ontario, Canada.

出版信息

Clin Immunol Immunopathol. 1998 Mar;86(3):280-9. doi: 10.1006/clin.1997.4479.

DOI:10.1006/clin.1997.4479
PMID:9557161
Abstract

Collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA) that can be regressed with Taxol (paclitaxel), a chemotherapeutic agent. To identify structural changes that occur with involution, the synovium from naive, untreated CIA, and Taxol-treated CIA rats were evaluated by light microscopy plus transmission and scanning electron microscopy. Analysis included detailed images of vascular networks using polymeric corrosion casts. The CIA synovium was morphologically similar to human RA synovium. In CIA, the integrity of the intimal lining is lost by Type-B synoviocytes becoming highly elongated and polarized toward the joint space, resulting in non-overlapping cellular processes and the elimination of the basal lamina. In addition, the lining expanded from a width of 6-10 microns in naives to 200-250 microns in CIA due primarily to increased numbers of both Type-A and -B synoviocytes and more interstitial matrix. Vascular corrosion casts of CIA synovium illustrated a marked increase in blood vessel volume and an extensive interconnecting vascular architecture; neovascular arrays were observed to project toward the synovial surface. In Taxol-treated CIA, the synoviocyte and neovascular components reverted to the naive synovium morphology, suggesting that this agent might be useful in the therapy of RA.

摘要

胶原诱导性关节炎(CIA)是类风湿性关节炎(RA)的一种动物模型,可被化疗药物紫杉醇消退。为了确定 involution 过程中发生的结构变化,通过光学显微镜以及透射和扫描电子显微镜对未处理的 CIA 大鼠、未处理的幼稚大鼠和紫杉醇处理的 CIA 大鼠的滑膜进行了评估。分析包括使用聚合物腐蚀铸型对血管网络进行详细成像。CIA 滑膜在形态上与人类 RA 滑膜相似。在 CIA 中,内膜衬里的完整性因 B 型滑膜细胞变得高度伸长并向关节腔极化而丧失,导致细胞突起不重叠且基膜消失。此外,内膜衬里的宽度从幼稚大鼠的 6 - 10 微米扩展到 CIA 大鼠的 200 - 250 微米,这主要是由于 A 型和 B 型滑膜细胞数量增加以及更多的间质基质。CIA 滑膜的血管腐蚀铸型显示血管体积显著增加且血管结构广泛相互连接;观察到新生血管阵列向滑膜表面突出。在紫杉醇处理的 CIA 中,滑膜细胞和新生血管成分恢复到幼稚滑膜的形态,表明该药物可能对 RA 治疗有用。

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Clin Rheumatol. 2019 Jan;38(1):19-27. doi: 10.1007/s10067-017-3646-1. Epub 2017 Apr 28.
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Paclitaxel suppresses collagen-induced arthritis: a reevaluation.紫杉醇对胶原诱导性关节炎的抑制作用:重新评估
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Angiogenesis as a target in rheumatoid arthritis.血管生成作为类风湿关节炎的一个治疗靶点。
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