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泪液明胶酶B活性与眼部酒渣鼻患者的IL-1α浓度及荧光素清除率相关。

Tear fluid gelatinase B activity correlates with IL-1alpha concentration and fluorescein clearance in ocular rosacea.

作者信息

Afonso A A, Sobrin L, Monroy D C, Selzer M, Lokeshwar B, Pflugfelder S C

机构信息

Ocular Surface and Tear Center, Bascom Palmer Eye Institute, Miami, FL 33136, USA.

出版信息

Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2506-12.

PMID:10509643
Abstract

PURPOSE

To correlate tear fluorescein clearance with interleukin-1alpha (IL-1alpha) concentration and gelatinase B (matrix metalloproteinase [MMP]-9) activity in the tear fluid of patients with ocular rosacea and normal control subjects.

METHODS

Gelatinase activity was evaluated by gelatin zymography in tear fluid obtained from 13 patients with ocular rosacea (including 1 patient with recurrent epithelial erosion, 2 with recurrent peripheral corneal infiltrates and vascularization, and 2 patients with epithelial basement membrane dystrophy) and 13 normal subjects with normal aqueous tear production and no irritation symptoms. Tear fluorescein clearance was evaluated by measuring fluorescence in tear fluid collected from the inferior meniscus 15 minutes after instillation of 5 microl of 2% Na-fluorescein with a CytoFluor II fluorometer. Pro-MMP-9 and IL-1alpha concentrations in the tear fluid were measured by enzyme-linked immunosorbent assay (ELISA).

RESULTS

Compared with normal control subjects, patients with ocular rosacea had a greater delay of tear fluorescein clearance (P < 0.001), a higher tear IL-1alpha concentration (P < 0.001), and a greater pro-gelatinase B (92 kDa) activity (P < 0.001) in their tear fluid. The 84-kDa active form of gelatinase B was observed in 46% of the rosacea tear samples and none of the controls. The zymographic results were confirmed by ELISA that showed a significantly greater concentration of pro-MMP-9 (92 kDa) in the tear fluid of rosacea patients than controls. Delayed tear clearance was correlated with elevated tear IL-1alpha concentration (p=0.67, P < 0.001) and increased tear gelatinase B activity (p=0.84, P < 0.001). Tear IL-1alpha concentration was correlated with tear gelatinase B activity (p=0.58, P < 0.002).

CONCLUSIONS

Gelatinase B (MMP-9) activity is greater in patients with ocular rosacea than in normal eyes. The majority of this activity is due to 92-kDa proform of this enzyme. This activity is correlated with delayed tear clearance and tear fluid concentration of interleukin-1alpha, a proinflammatory cytokine that has been reported to stimulate gelatinase B production. Elevated gelatinase B activity in ocular rosacea may be involved in the pathogenesis of the irritation symptoms, recurrent epithelial erosions, vascularization, and epithelial basement membrane dystrophy that develops in the corneas of patients with this condition.

摘要

目的

探讨眼部酒渣鼻患者与正常对照者泪液中荧光素清除率与白细胞介素-1α(IL-1α)浓度及明胶酶B(基质金属蛋白酶[MMP]-9)活性之间的相关性。

方法

采用明胶酶谱法评估13例眼部酒渣鼻患者(包括1例复发性上皮糜烂患者、2例复发性周边角膜浸润及血管化患者和2例上皮基底膜营养不良患者)及13例泪液分泌正常且无刺激症状的正常受试者泪液中的明胶酶活性。通过使用CytoFluor II荧光计,在滴入5微升2%的荧光素钠15分钟后,测量下泪弯月处采集的泪液中的荧光强度,以此评估泪液荧光素清除率。采用酶联免疫吸附测定法(ELISA)测量泪液中前MMP-9和IL-1α的浓度。

结果

与正常对照者相比,眼部酒渣鼻患者泪液荧光素清除延迟更明显(P<0.001),泪液IL-1α浓度更高(P<0.001),前明胶酶B(92 kDa)活性更强(P<0.001)。在46%的酒渣鼻患者泪液样本中观察到了84 kDa的明胶酶B活性形式,而对照组中均未观察到。酶谱分析结果通过ELISA得到证实,该结果显示酒渣鼻患者泪液中前MMP-9(92 kDa)的浓度显著高于对照组。泪液清除延迟与泪液IL-1α浓度升高相关(p=0.67,P<0.001),与泪液明胶酶B活性增加相关(p=0.84,P<0.001)。泪液IL-1α浓度与泪液明胶酶B活性相关(p=0.58,P<0.002)。

结论

眼部酒渣鼻患者的明胶酶B(MMP-9)活性高于正常眼。这种活性主要归因于该酶的92 kDa前体形式。这种活性与泪液清除延迟及促炎细胞因子白细胞介素-1α的泪液浓度相关,据报道白细胞介素-1α可刺激明胶酶B的产生。眼部酒渣鼻中明胶酶B活性升高可能参与了该病患者角膜出现的刺激症状、复发性上皮糜烂、血管化及上皮基底膜营养不良的发病机制。

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