基质金属蛋白酶抑制剂治疗碱烧伤后兔角膜融解的研究

目的研究基质金属蛋白酶抑制剂(GM 6001)在治疗兔角膜碱烧伤后角膜融解中的作用.方法将28只兔随机分为A、B组,将浸有2 mol/L(16只)及1 mol/L(12只)氢氧化钠的滤纸片分别置于A、B组兔右眼角膜上制备角膜重和中度碱烧伤模型;每组均设治疗和对照组,A、B治疗组术眼分别滴浓度为400及200 mg/L的GM 6001滴眼液,对照组滴药物基质液;均治疗30 d,然后处死动物.观察其角膜融解及混浊等情况,并进行病理组织学检查.结果 A组对照组8只兔眼角膜自伤后(13±5) d开始全部发生融解,2只兔眼发生角膜穿孔;治疗组,仅有2只兔眼烧伤后(19±4) d发生角膜融解,无角膜穿孔;两组角膜融解发生率及角膜穿孔率比较,差异有显著意义(P<0.05).治疗组角膜融解开始的时间亦明显迟于对照组(P＜0.05).B组对照组6只兔角膜自伤后(14±6) d全部融解,1只兔眼角膜穿孔;治疗组2只兔眼角膜自伤后(19±4) d融解,无角膜穿孔;两组角膜融解发生率间比较,差异有显著意义(P＜0.05);治疗组角膜混浊程度明显低于对照组(P＜0.01).病理检查结果显示治疗组角膜胶原纤维破坏轻,炎性细胞浸润明显少于对照组.结论 GM 6001可抑制和延迟碱烧伤后角膜融解的发生和发展,降低角膜胶原纤维的破坏及角膜组织中炎性细胞的浸润.

Experimental study on the treatment of corneal melting after alkali burn with GM 6001

OBJECTIVE: To eva1uate the effect of synthetic inhibitors of matrix metalloproteinases (GM 6001) on the prevention of melting of rabbit corneas after alkali burn. METHODS: Severe and moderate rabbit alkali burns were made by different concentrations of NaOH. Corneas with severe or moderate alkali injuries were topically treated with 400 mg/L or 200 mg/L GM 6001 for 30 days. Vehicle was used as control. All corneas were evaluated for melting, opacity and other pathological changes. RESULTS: After severe alkali burns, all of the 8 corneas of the control group melted in 13 +/- 5 days, and 2 corneas perforated. Only did 2 corneas melt in 19 +/- 4 days after burn and not perforate in 400 mg/L GM 6001 group. The rates of corneal melting and perforation in 400 mg/L GM 6001 group were lower than that of the control (P < 0.05), and the initial time of melting was later than that of the control (P < 0.0l). After moderate alkali burn, all of the 6 corneas of control melted in 14 +/- 6 days, and 1 cornea perforated. Only did 2 of 200 mg/L GM 6001 treated corneas melt in 19 +/- 4 days without perforation after burn. The rate of corneal melting and the degree of corneal opacity were lower in 200 mg/L GM 6001 treated than that of the control, the difference being significant (P < 0.0l). Histologic section of GM 6001 treated corneas revealed much less collagen fiber destruction and inflammatory cell infiltration than that of the control. CONCLUSION: GM 6001 not only can prevent and delay the corneal melting after alkali burn, but also can reduce the destruction of corneal collagen fibers and infiltration of inflammatory cells in the corneal tissue.