基质金属蛋白酶在实验性单纯疱疹性角膜炎中的分布表达

目的 明确角膜感染Ⅰ型单纯疱疹病毒(HSV—1)后基质金属蛋白酶(MMPs)及其组织抑制剂(TIMPs)在角膜中的分布。方法 HSV—1(KOS株)接种于BALB／c小鼠角膜上。分别收集正常眼球及感染后第2、7、14及28d的感染眼球行石蜡包埋，并应用抗MMP—2、—8、—9及TIMP—1、—2的抗体免疫染色角膜切片。结果 感染后第2d，MMP—2、—9及TIMP—1、—2的表达比未感染眼增加且表达主要位于浅表基质层及上皮下的炎性细胞中。感染后第14d及28d可见坏死性角膜炎及角膜溃疡形成，角膜基质中及浸润的炎性细胞中尤其是溃疡处可见MMP—2、—9及TIMP—1、—2表达显著增加。溃疡区域可见大量MMP—8阳性染色的中性粒细胞。结论 HSV—1角膜感染后由角膜细胞及浸润的炎性细胞分泌产生的MMPs对于上皮性角膜炎及溃疡形成过程可能起重要作用。

Localization of matrix metalloproteinases in experimental herpes simplex virus keratitis

Objective To determine the distribution of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in corneas with infection of herpes simplex virus type-1 (HSV-1). Methods Keratitis was induced in BALB/c mice by inoculating the cornea with HSV-1 ( KOS strain). Corneas were harvested at days 0,2 ,7 ,14 and 28 in post-infection (p. i. ). Corneal sections were immunostained with antibodies directed against MMP-2,MMP-9 ,MMP-8 ,TIMP-1 and TIMP-2. Results At day 2 in p. i. , MMP-2 and MMP-9 expression were increased in the superficial stroma and inflammatory cells beneath the epithelium. Similar staining patterns were detected for TIMP-1 and TIMP-2. Necrotizing keratitis with corneal ulceration was found on days 14 and 28 in p. i. This correlated with increased expression of MMP-2 and MMP-9 within the stroma and in infiltrating inflammatory cells. MMP-2, MMP-9 ,TIMP-1 and TIMP-2 staining was particularly intense in the proximity of the ulcers. The neutrophils, which were abundant at the site of ulceration,were stained positive with MMP-8. Conclusion Our data suggest that MMPs produced by resident corneal cells and inflammatory cells play a role in epithelial keratitis and ulcerative process of cornea after HSV-1 infection.