糖皮质激素对微血管产生直接毒性作用：细胞死亡机制分析。
Glucocorticoids exert direct toxicity on microvasculature: analysis of cell death mechanisms.
作者信息
El Zaoui Ikram, Behar-Cohen Francine, Torriglia Alicia
机构信息
*INSERM UMRS 1138, Team 17 from Physiopathology of Ocular Diseases to Clinical Developments, Paris, France, Pierre et Marie Curie University, Paris Descartes University, UMRS 1138, Centre de Recherche des Cordeliers 75006, Paris, France and Hopital Ophtalmique Jules Gonin 1000, Lausanne, Switzerland *INSERM UMRS 1138, Team 17 from Physiopathology of Ocular Diseases to Clinical Developments, Paris, France, Pierre et Marie Curie University, Paris Descartes University, UMRS 1138, Centre de Recherche des Cordeliers 75006, Paris, France and Hopital Ophtalmique Jules Gonin 1000, Lausanne, Switzerland *INSERM UMRS 1138, Team 17 from Physiopathology of Ocular Diseases to Clinical Developments, Paris, France, Pierre et Marie Curie University, Paris Descartes University, UMRS 1138, Centre de Recherche des Cordeliers 75006, Paris, France and Hopital Ophtalmique Jules Gonin 1000, Lausanne, Switzerland.
*INSERM UMRS 1138, Team 17 from Physiopathology of Ocular Diseases to Clinical Developments, Paris, France, Pierre et Marie Curie University, Paris Descartes University, UMRS 1138, Centre de Recherche des Cordeliers 75006, Paris, France and Hopital Ophtalmique Jules Gonin 1000, Lausanne, Switzerland *INSERM UMRS 1138, Team 17 from Physiopathology of Ocular Diseases to Clinical Developments, Paris, France, Pierre et Marie Curie University, Paris Descartes University, UMRS 1138, Centre de Recherche des Cordeliers 75006, Paris, France and Hopital Ophtalmique Jules Gonin 1000, Lausanne, Switzerland *INSERM UMRS 1138, Team 17 from Physiopathology of Ocular Diseases to Clinical Developments, Paris, France, Pierre et Marie Curie University, Paris Descartes University, UMRS 1138, Centre de Recherche des Cordeliers 75006, Paris, France and Hopital Ophtalmique Jules Gonin 1000, Lausanne, Switzerland *INSERM UMRS 1138, Team 17 from Physiopathology of Ocular Diseases to Clinical Developments, Paris, France, Pierre et Marie Curie University, Paris Descartes University, UMRS 1138, Centre de Recherche des Cordeliers 75006, Paris, France and Hopital Ophtalmique Jules Gonin 1000, Lausanne, Switzerland.
出版信息
Toxicol Sci. 2015 Feb;143(2):441-53. doi: 10.1093/toxsci/kfu243. Epub 2014 Dec 1.
Glucocorticoids (GCs) are routinely administered systemically or injected into the eye when treating numerous ocular diseases; however, their toxicity on the retinal microvasculature has not been previously investigated. In this article, the effects of hydrocortisone (Hydro), dexamethasone, dexamethasone-phosphate and triamcinolone acetonide (TA) were evaluated in vitro on human skin microcirculation cells and, bovine endothelial retinal cells, ex-vivo, on flat mounted rat retinas. The degree of GCs induced endothelial cell death varied according to the endothelial cell type and GCs chemical properties. GCs toxicity was higher in skin microvascular endothelial cells and for hydrophobic GC formulations. The mechanism of cell death differed between GCs, Hydro and TA activated the leukocyte elastase inhibitor/L-DNase II pathways but did not activate caspases. The mechanisms of cell death observed in cell cultures were similar to those observed in rat retinal explants. Taken together these results indicate that particular attention should be paid to the potential vascular side effects when administrating GCs clinically and in particular when developing sustained-release intraocular devices.
在治疗多种眼部疾病时，糖皮质激素（GCs）通常通过全身给药或眼内注射的方式使用；然而，其对视网膜微血管系统的毒性此前尚未得到研究。在本文中，氢化可的松（Hydro）、地塞米松、地塞米松磷酸钠和曲安奈德（TA）对人皮肤微循环细胞以及牛视网膜内皮细胞的体外作用，以及对大鼠视网膜平铺标本的离体作用得到了评估。GCs诱导内皮细胞死亡的程度因内皮细胞类型和GCs化学性质而异。GCs对皮肤微血管内皮细胞以及疏水性GC制剂的毒性更高。不同GCs导致细胞死亡的机制有所不同，Hydro和TA激活了白细胞弹性蛋白酶抑制剂/L - DNase II途径，但未激活半胱天冬酶。在细胞培养中观察到的细胞死亡机制与在大鼠视网膜外植体中观察到的相似。综上所述，这些结果表明，在临床使用GCs时，尤其是在开发缓释眼内装置时，应特别关注潜在的血管副作用。
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