基质金属蛋白酶-2特异性抑制剂1-（12-羟）18烷基硫酸钠抑制负透镜诱导豚鼠离焦性近视的发展

Inhibitory effects of Sodium 1- （ 12-Hydroxy）octadecanyl Sulfate, an MMP-2 inhibitor, on the development ofdefocus-induced myopia in guinea pigs

目的探讨基质金属蛋白酶-2（MMP-2）特异性抑制剂1-（12-羟）18烷基硫酸钠对负透镜诱导豚鼠离焦性近视形成的影响及其作用机制。方法对新生健康有色豚鼠随机分为3组，A组（10只）：右眼进行-IOD透镜诱导，左眼不作处理；B组（10只）：右眼透镜诱导＋抑制剂（9．0μg／ml，每3d结膜下注射），左眼不作处理；C组（10只）：右眼透镜诱导＋赋形剂，左眼不作处理，4周后测量屈光度，明胶酶谱法分析后部巩膜MMP-2活性，western—blot技术检测后部巩膜MMP-2的表达。结果豚鼠经4周负透镜诱导后，A组诱导眼较对侧眼增加了（5．73±0．36）D近视度；B组诱导眼较对侧眼增加了（2．58±0．33）D近视度；C组诱导眼较对侧眼增加了（6.31±0．73）D近视度；B组所获得的近视度低于A组和C组，差异有统计学意义（q检验，P〈0．05），A组和c组相比差异无统计学意义（P〉0．05）。B组抑制剂注射眼后部巩膜MMP-2活性成分低于A组和C组，差异有统计学意义（P〈0．05），酶原成分3组问比较差异无统计学意义（P〉0．05）。3组后部巩膜MMP-2蛋白水平差异无统计学意义（P〉0．05）。结论9．0μg／ml 1-（12-羟）18烷基硫酸钠，每3d结膜下注射可通过抑制后部巩膜MMP-2的活性，从而在-定程度上抑制新生豚鼠负透镜诱导离焦性近视的发展。

Objective To investigate the inhibitory effects of Sodium 1-（ 12-Hydroxy）octadecanyl Sulfate, an MMP-2 inhibitor, on the development of defocus-induced myopia in guinea pigs and its mechanism. Methods Thirty newborn guinea pigs were randomly divided into 3 groups,group A： -10D lens applied on right eye;group B： -10D lens and MMP-2 inhibitor treatment in right eye （9.0μg/ml, subconjunctival injection, every 3 days interval ） ;group C： -10D lens and vehicle treatment in right eye （same volume and frequency with those of group B ） ; there was no treatment in all the left eyes in this study.After 28 days of defocus, the refractive status was recorded and the posterior scleral sample was collected for MMP-2 zymography and western-blot analysis.Results The treated eyes of group A,B and C gained （5.73±0.36）D, （2.58±0.33）D and （6.31±0.73 ）D respectively,the amount of gained myopic refraction in eyes of group A was significantly less than that of eyes in group B and group C （P〈0.05） ; zymography analysis indicated that, of all the defocused animals, the activity of MMP-2 in the eyes treated by inhibitor was significantly lower than that of eyes treated by vehicle and no injected eyes, represented by the lower level of active MMP-2 （P〈0.05）;no significant difference was detected in the latent MMP-2 level between three groups （/）〉0.05 ） ; the MMP-2 protein level in posterior sclera of three groups also didn＇t show any significant difference by western-blot analysis （p〉0.05）.Conclusions 1-（ 12-Hydroxy）octadecanyl Sulfate（9.0μg/ml,subconjunctival injection,every 3 days interval）inhibited the development of defocus-induced myopia in newborn guinea pigs, may through, at least in part, in-hibitory effects on the activity of MMP-2 in posterior sclera.