基质金属蛋白酶抑制剂抑制兔晶状体后囊膜混浊的研究

摘要

目的 观察基质金属蛋白酶(MMP)抑制剂对兔晶状体后囊膜混浊的抑制作用和对眼内组织的毒性.方法 实验研究.选用新西兰白兔行超声乳化晶状体吸除术,用不同浓度的MMP抑制剂GM6001溶液(实验1组:100 μmol/L,实验2组:200 μmol/L,实验3组:500 μmol/L)和GM6001阴性对照液(500 μmol/L)进行术毕及术后隔日晶状体囊袋内灌注3次,观察术后第12周内后囊膜混浊情况,同时观察药物对眼前房反应、眼压、角膜内皮、虹膜、睫状体和视网膜的影响和毒性.采用四格表确切概率法分析使用GM6001后前房反应和对后囊膜混浊的抑制作用;采用单因素方差分析法分析GM6001对眼压的影响.结果 裂隙灯显微镜下观察,可见术后12周对照组后囊膜混浊明显,实验1组后囊膜混浊较对照组轻,实验2组和3组均无后囊膜混浊(P=0.007);病理学结果显示:对照组和实验1组后囊膜表面有多层排列紊乱的上皮细胞和成纤维细胞,而实验2组和3组后囊膜表面几乎无细胞生长;前房反应轻:用药2 d实验组和对照组兔眼前房闪光情况比较,差异无统计学意义(P=0.380);对眼压的影响:实验组与对照组用药2 d(F=0.642,P=0.597)、7 d(F=0.179,P=0.909)眼压比较,差异均无统计学意义;用药7 d,实验3组角膜内皮细胞呈规则的六边形,无变形脱落,与对照组眼角膜内皮细胞形态无明显差别;光镜观察发现对虹膜、睫状体和视网膜均无明显毒性.结论 MMP抑制剂可明显抑制兔眼超声乳化晶状体吸除术后晶状体后囊膜混浊的发生,对眼内组织无明显毒性,安全有效.%Objective To determine whether matrix metalloproteinase (MMP) inhibitor can provide therapeutic effects for rabbits posterior capsule opacification in vivo and to observe the side effects of this drug on surrounding intraocular structures. Methods Experimental research. New Zealand white rabbits were undertaken phacoemulsification operation. GM6001 at different concentrations ( 100,200 and 500 μmol/L)and GM6001 negative control liqueur were infused into the capsule bags of the rabbits at the end of operation and two days after the operation. The incidence of posterior capsule opacification was assessed and the histological sections of posterior capsules were observed under microscope 12 weeks after the surgery. The anterior chamber response was observed on day 2 post-operatively. The changes of intraocular pressure were measured by day 2 and day 7. Corneal endothelial cells were observed under scanning electron microscopeand iris, ciliary body and retina were observed under microscope on day 7. Results GM6001 significantly prevented posterior capsule opacification (P=0. 007 ). No opacification occurred on the rabbit posterior capsule in eyes with 200 and 500μmol/L GM6001 on week 12 post-operatively in vivo. No cells were found on posterior capsule in 500 μmol/L group, whereas lens epithelial cells and fibroblasts were found in the controls under microscope. No difference of anterior chamber flare between the eyes with GM6001 at different concentrations and the control group (P=0. 380) by day 2 after the operation. The intraocular pressure in eyes with GM6001 was the same as that in the control 2-days ( F = 0. 642, P = 0. 597 ) and 7-days ( F =0. 179 ,P =0. 909) post-operation. The corneal endothelial cells in eyes with 500 μ mol/L GM6001 arranged regularly and did not show any difference from that in the control eyes under scanning electron microscope 7-day after the operation. The iris, ciliary body and retina in eyes with 500 μmol/L GM6001 were normal in appearance 7-day after the operation. Conclusions MMP inhibitor can prevent posterior capsule opacification effectively in rabbits in vivo and does not cause damage to surrounding intraocular structures,suggesting that MMP inhibitor may become a medication used for the prevention of lens posterior capsule opacification.