Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea.
Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea.
复制标题
DOI：
10.1186/1471-2415-3-10
复制
发表时间：
2003-10-06
影响因子：
2
通讯作者：
O'Brien TP
中科院分区：
文献类型：
--
作者：
Reviglio VE;Hakim MA;Song JK;O'Brien TP
基质金属蛋白酶在细胞外基质沉积和降解中起重要作用。基于以往氟喹诺酮治疗角膜穿孔的临床观察，我们决定比较评价不同氟喹诺酮滴眼液对角膜基质金属蛋白酶（MMPs）表达的影响。将80只雌性Lewis大鼠分为角膜上皮完整组和损伤组。在右眼组织中心应用75%酒精6秒，形成均匀的角膜上皮缺陷。各组泪液：羧甲基纤维素钠0.5% (Refresh, Allergan)；2)环丙沙星0.3%（西洛昔、爱尔康）；3)氧氟沙星0.3%(Ocuflox, Allergan)；4)左氧氟沙星0.5%（Quixin, Santen）。滴眼液每天6次，持续48小时。48小时处死大鼠。使用mmp -1、2、8和9特异性抗体进行免疫组织化学分析和酶谱分析。局部氟喹诺酮类药物治疗48小时后检测未清除角膜上皮组中MMP-1、MMP-2、MMP-8和MMP-9的表达。0.3%环丙沙星、0.3%氧氟沙星、0.5%左氧氟沙星组MMPs的定量表达无统计学差异。将人工撕裂组与角膜上皮缺损氟喹诺酮组进行比较，观察到伤口愈合过程中MMPs的表达增加。然而，氟喹诺酮治疗组表现出具有统计学意义的高水平MMPs表达。本研究初步证明，与人工泪液眼液相比，局部应用氟喹诺酮类药物可诱导角膜上皮中MMP-1、MMP-2、MMP-8和MMP-9的表达。
Matrix metalloproteinases play an important role in extracellular matrix deposition and degradation. Based on previous clinical observations of corneal perforations during topical fluoroquinolone treatment, we decided to evaluate the comparative effects of various fluoroquinolone eye drops on the expression of matrix metalloproteinases (MMPs) in cornea. Eighty female Lewis rats were divided into two experimental groups: intact and wounded corneal epithelium. Uniform corneal epithelial defects were created in the right eye with application of 75% alcohol in the center of the tissue for 6 seconds. The treatment groups were tested as follows: 1) Tear drops: carboxymethylcellulose sodium 0.5 % (Refresh, Allergan); 2) Ciprofloxacin 0.3% (Ciloxan, Alcon); 3) Ofloxacin 0.3%(Ocuflox, Allergan); 4) Levofloxacin 0.5%(Quixin, Santen). Eye drops were administered 6 times a day for 48 hours. Rats were sacrificed at 48 hours. Immunohistochemical analysis and zymography were conducted using antibodies specific to MMPs-1, 2, 8 and 9. MMP-1, MMP-2, MMP-8 and MMP-9 expression were detected at 48 hrs in undebrided corneal epithelium groups treated with the topical fluoroquinolones. No statistical difference was observed in quantitative expression of MMPs among ciprofloxacin 0.3%, ofloxacin 0.3%, levofloxacin 0.5%. When the artificial tear group and the fluoroquinolone groups with corneal epithelial defect were compared, increased expression of MMPs was observed as a result of the wound healing process. However, the fluoroquinolone treated group exhibited high statistically significantly levels of MMPs expression. Our study provides preliminary evidence that topical application of fluoroquinolone drugs can induce the expression of MMP-1, MMP-2, MMP-8 and MMP-9 in the undebrided corneal epithelium compared to artificial tear eye drops.