基质金属蛋白酶及其组织抑制剂在糖尿病小鼠视网膜组织中的表达

目的:探讨基质金属蛋白酶(MMP-2、MMP-9)及其组织抑制剂(TIMP-2)在糖尿病视网膜病变(DRP)发生发展中的作用及其机制。方法:用免疫组织化学方法和计算机-图像分析技术研究C57BL/KsJdb/db糖尿病小鼠视网膜组织中MMP-2、MMP-9和TIMP-2的表达情况,并观察糖尿病小鼠视网膜毛细血管及其基底膜的超微结构改变,其db/ 型同性同窝瘦型鼠为对照;用SAS软件对实验结果进行统计学处理。结果:随病程进展,糖尿病小鼠视网膜毛细血管基底膜进行性增厚,MMP-2和MMP-9在糖尿病小鼠视网膜组织中的表达显著性降低(P <0.05),而TIMP-2的表达显著性升高(P <0.05),同一病程阶段的MMP-2/TIMP-2的比值显著性降低(P <0.05)。结论:随着病程进展,由于TIMP-2表达的增高,通过与MMP-2以1:1的比例结合成复合物的形式抑制了MMP-2的活性,另外又有MMP-9的表达随病程进展显著下降,这可能是导致DRP早期视网膜毛细血管基底膜进行性增厚的原因。     

基质金属蛋白酶2及其抑制剂在大鼠青光眼滤过术后滤过泡组织中的动态表达

背景 青光眼滤过术后瘢痕形成是导致手术失败的主要原因,探讨球结膜滤过泡中基质金属蛋白酶2(MMP-2)及组织金属蛋白酶抑制剂2(TIMP-2)的表达对于术后瘢痕形成的发病机制研究具有重要意义. 目的 观察大鼠球结膜滤过泡模型滤过区组织中MMP-2及TIMP-2的表达与瘢痕形成进程的关系.方法 采用完全随机化分组法将63只6～8周龄清洁级雄性SD大鼠分为正常对照组和术后1、3、5、7、14、28 d组,每只大鼠任选一侧眼为实验眼.采用前房引流管植入术建立大鼠球结膜滤过泡模型,术后裂隙灯显微镜下观察大鼠球结膜滤过泡的形成情况及眼前节反应,各组于相应时间点颈椎脱臼法处死大鼠,其中3只眼制备完整眼球冰冻切片,采用免疫荧光化学染色法检测标本中MMP-2及TIMP-2的表达和定位;另取6只大鼠结膜滤过区组织行Western blot检测,观察MMP-2和TIMP-2在滤过区组织中的动态表达. 结果 所有术眼在术后第1天均形成不同程度隆起的滤过泡,维持时间为7 ～17d,平均生存时间为12d.Western blot检测结果显示,正常对照组大鼠滤过区组织中MMP-2蛋白的相对表达量为121.67±4.37,在术后3d组开始逐渐增高,为183.67±5.61,术后7d组达峰值,为230.50±8.48,随后逐渐降低,术后28 d组为172.33±8.43,仍高于正常对照组,各组大鼠滤过区组织中MMP-2蛋白的相对表达量总体比较差异有统计学意义(F=280.18,P＜0.05).正常对照组大鼠滤过区组织中TIMP-2蛋白的相对表达量为102.50±6.25,在术后3d组开始明显升高,为162.67±7.00,术后5d组TIMP-2蛋白表达量达峰值,为232.00±11.03,之后逐渐下降,术后28 d组降至150.50±6.41,但仍高于正常对照组,各组间滤过区组织中TIMP-2蛋白的相对表达量的总体比较差异有统计学意义(F=145.34,P＜0.05).免疫荧光组织化学结果显示,正常对照组MMP-2、TIMP-2仅在大鼠结膜上皮层微弱表达,呈红色荧光,而在术后大鼠滤过区结膜组织上皮层和固有层均呈强荧光. 结论 MMP-2和TIMP-2在大鼠青光眼滤过术后滤过区组织的动态表达与滤过泡的纤维化过程相一致,提示MMP-2和TIMP-2参与结膜滤过泡的瘢痕化过程.     

TIMP-2基因转染豚鼠巩膜成纤维细胞基质金属蛋白酶2及其抑制剂表达

目的观察转染基质金属蛋白酶2抑制剂(tissue inhibitor of matrix metalloproteinase2,TIMP-2)基因的豚鼠巩膜成纤维细胞不同时间增生能力及基质金属蛋白酶2(matrix metalloproteinase2,MMP-2)和TIMP-2的表达,探讨基因治疗近视的可行性。方法随机选取三色健康豚鼠,组织块法体外培养原代巩膜成纤维细胞,免疫组织化学法进行波形蛋白的鉴定,取第3～6代细胞进行实验。分子克隆构建携带TIMP-2基因的真核表达载体,转染豚鼠巩膜成纤维细胞,MTT法观察转染后12h、24h、48h、3d、5d、7d细胞增生能力。提取总RNA,二步法逆转录-聚合酶链反应检测MMP-2mRNA及TIMP-2mRNA的表达水平。结果豚鼠巩膜成纤维细胞原代、传代培养生长良好,波形蛋白鉴定阳性。转染3d、5d、7d TIMP-2基因转染组成纤维细胞的增生速度分别为0.6724±0.0092、0.7963±0.0060、0.8462±0.0064,明显快于正常对照组成纤维细胞(0.5810±0.0120、0.6525±0.0072、0.7129±0.0132),差异均具有显著统计学意义(均为P<0.01)。转染48h MMP-2mRNA表达即开始减少,转染3d时表达明显减少,达到最低,除转染12h与24h之间外,转染组与正常对照组、各转染不同时间组间MMP-2mRNA表达差异均有统计学意义(均为P<0.05)。TIMP-2mRNA表达在转染48h时即开始增加,除12h与24h外,转染组与正常对照组、各转染不同时间组间TIMP-2mRNA表达差异均有统计学意义(均为P<0.05)。结论转染TIMP-2基因对豚鼠巩膜成纤维细胞有促增生作用,TIMP-2基因转染豚鼠巩膜成纤维细胞抑制MMP-2mRNA的表达,可在一定程度上阻止近视发展中巩膜组织的丢失与重塑。     

基质金属蛋白酶及其组织抑制剂与白内障

基质金属蛋白酶(matrixmetalloproteinases,MMPs)是一类金属依赖的水解酶家族,是细胞外基质(extracelluarmatrix,ECM)降解的主要介质,其主要功能是降解细胞外基质,在细胞迁移、组织重建和修复等病理生理过程中发挥作用。MMPs的蛋白水解活性主要靠与其抑制剂(tissueinhibitorofMMPs,TIMPs)之间平衡来调节。近年来研究表明,MMPs/TIMPs功能异常同眼部许多疾病有关,如原发开角型青光眼、白内障、翼状胬肉、年龄相关性黄斑变性等有关。     

基质金属蛋白酶及其抑制剂在眼表疾病发病机制研究中的进展

基质金属蛋白酶(matrix metalloproteinases,MMPs)是一组降解细胞外基质的内源性蛋白酶系,其与基质金属蛋白酶组织抑制剂(tissue inhibitor of metalloproteinases,TIMPs)组成MMPs/TIMPs系统,降解和重塑细胞外基质.MMPs/TIMPs系统表达水平的失衡与眼病的发生发展密切关联,尤其是在各类眼表疾病中.目前认为结膜成纤维细胞中MMP-1、MMP-3及MMP-9过度表达是引起MMPs与TIMPs之间失去平衡的关键因素.MMPs与TIMPs之间失去平衡,使胶原纤维融解,弹力纤维变性减少,导致球结膜基质和Tenon囊的过度降解,引起眼表泪液异常的病理循环.眼表泪液的异常破坏了眼表环境的稳定性,参与多个眼表疾病如干眼、结膜松弛症、翼状胬肉、角膜炎等的病理变化.     

基质金属蛋白酶及其抑制剂与眼部疾病

基质金属蛋白酶(MMPs)是一组锌离子依赖性内肽酶，其主要功能是降解细胞外基质，在细胞迁移、组织重建和修复等病理生理过程中发挥作用。MMPs的蛋白水解活性主要靠与其抑制剂TIMPs之间的平衡来调节。尽管MMPs和TIMPs参与的具体机理尚未明确，但对于寻找角膜炎、白内障、青光眼及增生性玻璃体视网膜病变等眼病的发病机理有重要意义。本文综述了MMPs、TIMPs在眼病中的表达变化及作用。     

豚鼠形觉剥夺早期后极部巩膜基质金属蛋白酶2及其抑制剂动态表达

目的探讨豚鼠形觉剥夺性近视（form-deprivation myopia, FDM ）早期后极部巩膜基质金属蛋白酶2（matrix metalloproteinase-2, MMP-2）及基质金属蛋白酶抑制剂2（tissue inhibitor of matrix metalloproteinase-2,TIMP-2）mRNA的表达。方法4周龄三色豚鼠50只,随机分成实验组和正常对照组各25只,实验组又随机分为5组,单眼形觉剥夺（monocular deprivation, MD）右眼1、4、7、14、21d制备FDM动物模型,未遮盖眼为自身对照组。各组豚鼠进行检影验光和A超测量眼轴长度。提取后极部巩膜总RNA,二步法逆转录聚合酶链反应检测各组后极部巩膜MMP-2及TIMP-2mRNA的表达水平。结果除1d外,各组MD后极部巩膜MMP-2mRNA的表达与正常对照组、自身对照组差异均有统计学意义（P〈0,05）,MD组间差异也有统计学意义（P〈0．01）;而TIMP-2mRNA的表达则逐渐下降。各自身对照组MMP-2、TIMP-2mRNA的表达与MD组变化趋势大致相同。结论MMP-2／TIMP-2之间动态平衡失调可能是启动豚鼠FDM巩膜细胞外基质早期主动重塑的重要因素。（中国跟耳鼻喉科杂志,2010,10：75—78）     

基质金属蛋白酶抑制剂抑制兔晶状体后囊膜混浊的研究

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.

Abstract：

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.     

基质金属蛋白酶抑制剂抑制兔晶状体后囊膜混浊的研究

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.     

基质金属蛋白酶抑制剂抑制兔晶状体后囊膜混浊的研究

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.     

巩膜细胞外基质及基质金属蛋白酶在近视发展中作用的研究进展

近视是眼科发病率最高的疾病,目前尚无明确有效的防治方法。近年来研究表明：近视的发生发展与巩膜细胞外基质（ECM）的重塑有密切关系,而基质金属蛋白酶（MMPs）作为调节巩膜ECM动态平衡最重要的一大酶系,其活性增加与近视发展明显相关。本文就目前巩膜ECM及MMPs在近视发展中作用的研究进展进行综述。     

三种视网膜病视网膜前膜中基质金属蛋白酶及其天然抑制分子的表达

目的 研究增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)、增殖性玻璃体视网膜疾病(proliferative vitreoretinopathy,PVR)和急性视网膜坏死(acute retinalnecrosis,ARN)患者视网膜前膜中基质金属蛋白酶(matrixmetalloproteinases:MMPs)及其天然抑制物(tissueinhibitorsofmetalloproteinages,TIMPs)的表达情况.方法 玻璃体手术中剥取PVR、PDR和ARN患者的视网膜前膜,同供体眼视网膜作为正常对照,冰冻切片后进行免疫组织化学染色,包括:MMP-1,MMP-2,MMP-3,MMP-7,MMP-9,TIMP-1和TIMP-2.结果 正常视网膜中能够观察到MMP-1,MMP-3,TIMP-1和TIMP-2的表达,在PVR、PDR和ARN患者标本中各种分子的表达都增强,尤以MMP-2,MMP-3和MMP-7明显.结论 正常视网膜中存在MMPs和TIMPs分子维持着细胞外基质动态的平衡,在PVR,PDR和ARN患者中MMP-2,MMP-3和MMP-7等MMPs分子表达增强,在其病变过程中可能起重要作用.     

Matrix metalloproteinases (MMP-2 and 9) and tissue inhibitors of matrix metalloproteinases (TIMP-1 and 2) during the course of experimental necrotizing herpetic keratitis

To determine the distribution and activities of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) during the course of experimental herpes simplex virus (HSV) type-1 keratitis, BALB/c mice were corneally infected with 10(5) plaque-forming units (PFU) of HSV-1 (KOS strain) and then observed for the clinical signs of keratitis. Corneas were harvested at days 0, 2, 7 and 14 post-infection (p.i.). MMP-2, MMP-9, MMP-8, TIMP-1 and TIMP-2 were detected by immunohistochemistry and the Western blot technique. The enzymatic activities were analyzed by zymography. Epithelial HSV keratitis was present at day 2 after corneal infection and healed by day 5 p.i. While the expression and activity of MMP-2, MMP-8 and MMP-9 increased in the corneas at day 2 p.i., it was reduced at day 7 p.i. TIMP-1 and -2 were expressed in the corneas before and seven days after infection. Necrotizing stromal keratitis with corneal ulceration and dense polymorphonuclear leukocyte (PMN) infiltration was present at day 14 p.i. This correlated with increased expression of MMP-2, MMP-8 and MMP-9 in the corneas. MMP-8, MMP-9 and MMP-2 staining was particularly intense in the proximity of the ulcers and in areas of PMN infiltration. At day 14 p.i., MMP-2, -8 and -9 activities were upregulated, and TIMP-2 was expressed. These data suggest that MMPs produced by resident corneal cells and PMNs may possibly play a role in early epithelial keratitis and in the ulcerative process in the late phase after corneal HSV-1 infection. The ratio of MMPs to TIMPs may be important for the course of necrotizing HSV keratitis. TIMPs might participate in the repair process.     

家兔晶状体机械性损伤后虹膜和房水中组织金属蛋白酶抑制物活性的改变

目的　探讨家兔晶状体机械性损伤后 ,基质金属蛋白酶抑制物 (TIMPs)在虹膜组织和房水中的动态变化及其意义。方法　建立单眼晶状体机械性损伤的家兔模型 ,应用反向酶谱法检测并定量分析损伤后 1、3、7和 15d眼内虹膜组织和房水中两种主要的TIMPs (TIMP 1、2 )的活性 ,并应用蛋白酶谱法检测TIMPs的作用底物基质金属蛋白酶 (MMPs)的活性。结果　健康家兔眼和实验家兔未损伤眼的虹膜组织和房水中 ,均未检测到TIMP 1、2的相应蛋白活性条带。伤后 1d家兔损伤眼的虹膜组织中的TIMP 1、2活性显著增加 (P <0 0 5 ) ,而MMP 2的活性受抑制 ;伤后 1d损伤眼的房水中 ,TIMP 1、2的活性均显著增加 (P <0 0 5 ) ;此后逐渐减少 ,至伤后 7d与健康家兔比较无差异 (P值分别为 0 0 97和 0 777) ;酶谱分析结果显示MMP 2活性的改变与此对应 ,即在损伤后 1d受到抑制 ,此后逐渐恢复。结论　TIMPs参与家兔晶状体机械性损伤后的眼内急性反应 ,对抑制炎性反应、促进创伤修复可能具有重要意义。     

体外培养猴眼小梁细胞及睫状肌细胞中组织金属蛋白酶抑制剂的表达

目的：观察体外培养的正常猴眼小梁细胞及睫状肌细胞中组织金属蛋白酶抑制剂（tissue inhibitors of metalloproteinase,TIMP)的表达,探讨生理状态下基质金属蛋白酶（matrix metalloproteinase,MMP)及TIMP在小梁网房水流出及葡萄膜－巩膜房水流出的通道中的作用。方法：采用Reverse-zymography技术,检测猴眼小梁细胞及睫状肌细胞中TIMP及MMP的表达。结果;猴眼小梁细胞及睫状肌细胞培养液中均可见TMIP－1、TIMP－2及TIMP－3表达,小梁细胞中MMP／TIMP比值明显高于睫状肌细胞。结论：正常状态下小梁细胞外基质的降解能力明显高于睫状肌细胞,可能是由于传统的小梁网房水流出通道作用强于葡萄膜－巩膜房水流出通道 的作用。     

增生性玻璃体视网膜病变增生膜中基质金属蛋白酶及其抑制剂的表达

目的研究增生性玻璃体视网膜病变（proliferative vitreoretinopathy，PVR）增生膜中基质金属蛋白酶（matrix metalloproteinases，MMP）及其抑制剂（tissue inhibitors of matrix metalloproteinases，TIMP）的表达。方法采用免疫组织化学技术的SP法，检测PVR增生膜和正常尸眼神经视网膜标本中MMP-2、MMP-9和TIMP-1的表达，光镜观察染色结果。结果41例PVR增生膜标本HE染色切片光镜下可见视网膜色素上皮（retinal pigment epithelial，RPE）细胞、神经胶质细胞、成纤维细胞、巨噬细胞等细胞成分，它们被大量细胞外基质所包绕。视网膜前膜中以RPE细胞为主要增生细胞，视网膜下膜中以神经胶质细胞为主要增生细胞。免疫组织化学染色结果显示：（1）25例PVR增生膜标本表达MMP-2，11例PVR增生膜标本表达MMP-9，14例PVR增生膜标本表达TIMP-1；（2）22例视网膜前膜标本表达MMP-2，3例视网膜下膜标本表达MMP-2，差异有显著性（P〈0．05）；（3）正常尸眼神经视网膜标本中未检测到MMP-2、MMP-9及TIMP-1的表达。结论细胞外基质与PVR增生膜的形成关系密切，MMP-2、MMP-9及TIMP-1在PVR形成过程中发挥重要作用，通过合理地调控MMP和TIMP的平衡，为预防和治疗PVR提供可能性理论依据。     

兔眼IOL术后基质金属蛋白酶抑制因子在虹膜、晶状体上皮细胞的表达

目的　探讨白内障囊外摘出及人工晶状体植入术后基质金属蛋白酶抑制因子 (TIMPs)在虹膜、晶状体上皮细胞的表达和TIMPs对后囊膜混浊的形成及纤维化的影响。方法　取 2 5只健康成年家兔 ,均一只眼行晶状体囊外摘出及人工晶状体植入术 ,另一眼作为对照组。每 5只兔眼为一组 ,分别于术后 1、3、7、14、3 0d取出虹膜和晶状体上皮细胞 ,用RT PCR和反向酶谱分析法检测各标本中的TIMPsmRNA和蛋白质的表达 ,并用羟脯氨酸试剂盒检测晶状体囊膜羟脯氨酸量的变化。结果　在正常虹膜、晶状体上皮细胞组织均有TIMP 1、 2、 3和 4mRNA的表达 ,而无相对蛋白质活性的表达 ;术后第 1d ,TIMP 1、 2、 3和 4mRNA即出现明显升高 ,其中术后第 7d ,TIMP 1和 2mRNA的表达量为最大 ,此后逐渐下降 ,术后第 3 0d的表达量仍高于对照组 (P <0 0 5 ) ;TIMP 3mRNA轻度升高 ,TIMP 4mRNA则轻度下降 ;羟脯氨酸的含量于术后 1、3、7d和 14d明显低于术后 3 0d(P <0 0 5 )。结论　TIMPs可能是抑制白内障囊外摘出及人工晶状体植入术后细胞外基质降解的主要因素 ,还可能是后囊膜混浊的形成和纤维化的重要原因之一。     

猴实验性青光眼视乳头筛板细胞外基质免疫组化研究

目的 研究猴实验性青光眼视乳头筛板细胞外基质的改变,探讨眼压增高对筛板的影响。方法 用免疫过氧化物酶技术J（ABC法）观察9只猴早、中、晚期青光眼模型筛板中,Ⅳ型胶原蛋白、层连接蛋白的分布。结果 与正常猴视乳头相比,早、中期青光眼模型视乳头筛板无明显变化。晚期青光眼视乳头筛板前区和筛板部Ⅳ型胶原蛋白和层连接蛋白阳性染色物明显增多,筛板后陷、重叠及融合。结论 青光眼病理过程中的眼压增高,可引起视乳头筛板细胞外基质发生特异性改变,从而使视乳头筛板的生物力学特性发生变化。     

Time-dependent matrix metalloproteinases and tissue inhibitor of metalloproteinases expression change in fusarium solani keratitis

AIM: To investigate matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression during the progress of fusarium solani (F.solani) keratitis in a rat model. METHODS: A rat model of F.solani keratitis was produced using corneal scarification and a hand-made contact lens. MMPs and TIMPs expressiond were explored in this rat model of F.solani keratitis using real-time polymerase chain reaction (PCR) and DIF. GM6001 (400 μmol/mL) was used to treat infected corneas. The keratitis duration, amount and area of corneal neovascularization (CNV) were evaluated. RESULTS: MMP-3 expression was 66.3 times higher in infected corneas compared to normal corneas. MMP-8, -9, and -13 expressions were significantly upregulated in the mid-period of the infection, with infected-to-normal ratios of 4.03, 39.86, and 5.94, respectively. MMP-2 and -7 expressions increased in the late period, with the infected-to-normal ratios of 5.94 and 16.22, respectively. TIMP-1 expression was upregulated in the early period, and it was 43.17 times higher in infected compared to normal corneas, but TIMP-2, -3, and -4 expressions were mildly downregulated or unchanged. The results of DIF were consistent with the result of real-time PCR. GM6001, a MMPs inhibitor, decreased the duration of F.solani infection and the amount and area of CNV. CONCLUSION: MMPs and TIMPs contributed into the progress of F.solani keratitis.