【作者】 申家泉；

【导师】 吴欣怡；

【作者基本信息】 山东大学 ， 眼科学， 2005， 博士

【摘要】 目的:研究基质金属蛋白酶抑制剂GM6001能否抑制青光眼滤过手术后瘢痕形成。 方法:通过随机、双盲、前瞻性的研究,将24只(48眼)新西兰大白兔随机分为4组,行青光眼滤过手术。其中3组(每组12只眼)。分别接受不同浓度GM6001 (3000μM、2000μM、1000μM)棉片放置于巩膜床、结膜和筋膜囊下5分钟,1组为对照组(12眼),不用药。观察手术后滤过泡存留的时间,术后外观、眼压等变化。术后32天杀死动物,行病理检查。 结果:GM6001治疗组的滤过泡存留时间明显延长。在第15天(平均11天),对照组的11只眼(死亡1只)(100%)手术全都失败,而用GM6001处理的实验组A(3000μM,5min)12眼滤过泡存活平均30天(28-32天)。实验组B11眼(死亡1只)(2000μM,5min)滤过泡存留时间平均是26.5天(24-28天),而实验组C(1000μM是21.5天(14-24天)。用卡-迈曲线(时序检验,P<0.001)分析两组间滤泡存留率,A组与B组间无显著性差异(P>0.05);A组和B组均与C组有显著性差异(P<0.01);A、B、C三组均与对照组有显著性差异(P<0.01)。GM6001实验组的眼压始终比对照组低(P<0.01)。GM6001实验组的手术区瘢痕组织比对照组明显减少。更多还原

【Abstract】 PURPOSE: To determine whether application of a broad-spectrum matrix metalloproteinase (MMP) inhibitor, GM6001, could reduce scarring after glaucoma filtration surgery.METHODS: In a randomized, prospective, masked-observer study, 24 New Zealand White rabbits underwent glaucoma filtration surgery. The animals were randomly allocated to 4 groups, 3 receive GM6001 cotton swab of 3000μM, 2000μM, 1000μM for 5 minutes, respectively, and 1 receive nothing during the operation. The animals were killed on days 30. Clinical characteristics, which included bleb morphology and intraocular pressure, were recorded. Tissue sections were HE stainedRESULTS: The presence of bleb was significantly prolonged in the GM6001-treated group compared with the control group(P < 0.001). The blebs had survived to day average 30 (28-32),in the GM6001-treated groupA(3000μM); the bleb of GM6001-treated group B survived to average 26.5(24-28); for GM6001-treated group C, the bleb suevived to average 21.5(14-24),whereas no blebs survived to day 15 (average 11) for the control group . The intraocular pressure remainedsignificantly lower throughout the course of the experiment in the GM6001 group compared with the control group (P < 0.001). Histologically, less scar tissue was observed at the trabeculectomy site with inhibition of MMP, compared with control group.CONCLUSIONS: This study suggested that the healing response after surgery can be modulated by inhibiting effects of MMPs. Inhibition of MMP significantly improved surgical outcome by reducing the amount of scar tissue produced. By targeting the actions of these proteolytic enzymes, a more controlled and physiological method of modulating scarring may be achieved.Objective : To determine the expression and distribution of matrix metalloproteinase(MMP-l,2,3,7,9) and their tissue inhibitors of metalloprotein-ases(TIMP-l,2,3,4)in normal human iris, ciliary body, choroid , retina pigmentary epithelium.Methods: . Immunofluorescent SABC-Cy3 method was used to investigate the expression of MMP-1,2,3,7,9 and TIMP-1,2,3,4 in iris, ciliary body, choroid and RPE from normal human eyes.Results: l.In the iris, staining intensity generally followed this pattern: anterior border>anterior epithelium>iris stroma>posterior epithelium. In anterior border, staining for MMP-1,2,3 and TIMP-1 was stronger than that of MMP-7,9 and TIMP-2,3,4; in anterior epithelium, staining for MMP-2 was heavier than that of other antibodies; in the stroma and posterior epithetlium all staining was slight.2. In the ciliary body, the patterns of intensity of the staining was non-pigmentepithelium >ciliary muscle >pigment epithelium >stroma for all antibodies. In the non-pigmentepithelium, pigment epithelium and stroma the staining for MMP-1,2,3 and TIMP-3 was heavier than that for MMP-3,7,9 and TIMP-1,2,4, but in the ciliary muscle MMP-2 and TIMP-2,3 staining was stronger than other staining. Whereas staining for MMP-1,2,3,7,9 and TIMP-1,2,4 was mainly in the cytoplasm of both non-pigment epithelium and pigment epithelium cells.staining for TIMP-3 was mostly in the basement membrane of the epithelium.3. In the choroid, all saining was moderately strong, but the staining for MMP-1,2 and TIMP-1 was sligtly stronger than that for other antibodies.4. The staining for MMP-1,2,3,7,9 and TIMP-1,2,3,4 was seen in the RPE. In the RPE, the staining for MMP-1,2,3,7,9 and TIMP-1,2,3,4 was all apparent.Conclusions: In normal eyes, staining for MMP-1,2,3,7,9 and TIMP-1,2,3,4 was observed in the iris, ciliary body, choroid , retina pigmentary epithelium, although there was marked variation in the intensity of staining in different regions. And there are certain expression patterns in some parts.Objective : To determine the expression and distribution of matrix metalloproteinase(MMP-l,2,3,7,9) and their tissue inhibitors of metal loprotein-ases(TIMP-l,2,3,4)in normal human retina and optic nerve .Methods: Immunohistochemical SP method was employed to detect the expression and distribution of MMP-1,2,3,7,9 and TIMP-1,2,3,4 in, retina, optic nerve from normal human eyes.Results: The staining for MMP-1,2,3,7,9 and TIMP-1,2,3,4 was seen in the neurosensory retina . In the neurosensory retina, the staining for MMP-1,2,3 and TIMP-1,2,3,4 was strong and there was differences in the staining intensity for these seven antibodies; the staining for MMP-7 and MMP-9 was observeved mostly in the ganglion cells and rod and cone, but the former was strong and the latter was very slight. For MMP-7 ,the stainig in outer segment was stronger than that in inner segment, while for other MMPs and TIMPs, the staining in inner segment was stronger than that in outer segment.In the optic nerve, apparent staining was observed mostly in the nerve fibers and glial cells. In the nerve fibers, staining for MMP-1 was strong, stainig for MMP-2 and TIMP-1,2,3,4 was slight ,and staining for MMP-3,7,9 was the slightest. And in the cytoplasme of glial cells ,staining for MMP-1,3 was the strongest, for MMP-2 and TIMP-1,2,3,4 was slight, for MMP-9 was the slightest and for MMP-7 was unseen.Conclusions: In normal eyes, staining for MMP-1,2,3,7,9 and TIMP-1,2,3,4 wasobserved in the retina, optic nerve without obvious specificity , although there was marked variation in the intensity of staining in different regions. And there are certain expression patterns in some parts.更多还原