Lat-B对家兔巩膜胶原重塑的影响  

Effects of latrunculin-B on rabbit sclera collagen remodeling

作　　者：李卫国[1] 张磊[1] 宫月荣[1] 雷宁玉[1] 考华婷[1] 何湘珍[2] 

机构地区：[1]滨州医学院附属医院眼科,256600 [2]南华大学第二附属医院眼科,衡阳411000

出　　处：《眼科研究》2010年第11期1048-1053,共6页Chinese Ophthalmic Research

基　　金：湖南省卫生厅资助项目(B2005105)

摘　　要：目的研究latrunculin-B(Lat-B)对兔巩膜通透性的影响,为细胞骨架因子在青光眼治疗中的应用及眼后节疾病的药物传递研究提供新的思路和理论依据。方法 36只家兔随机分为平衡盐液(BSS)组、二甲基亚砜(DMSO)组及Lat-B组,每组12只,分别用BSS、DMSO和Lat-B局部点眼,于用药前1h及用药后1、2、3、4、5、6、24h分别测量眼压,于24h后处死动物并获取部分巩膜组织,自制巩膜滤过装置测试巩膜通透性的变化,部分巩膜组织行免疫组织化学染色以检测前部巩膜组织中基质金属蛋白酶-2(MMP-2)和组织金属蛋白酶-2抑制剂(TIMP-2)的表达。光学显微镜下观察实验兔眼部各组织结构的形态学变化。结果 Lat-B组、BSS组与DMSO组点眼前后各时间点眼压的总体变化差异有统计学意义(F=25.76,P<0.01),Lat-B点眼后不同时间点与点眼前比较眼压呈下降趋势,差异有统计学意义(Ftime=4.50,P<0.01),点眼后1h即可引起眼压降低,降眼压作用可持续24h;BSS组与DMSO组点眼前后各时间点眼压变化的差异无统计学意义(P>0.05);Lat-B点眼后的前部巩膜对BSS的滤过较BSS组和DMSO组明显增加,3组的总体比较差异有统计学意义(F=47.50,P<0.01);Lat-B组、BSS组和DMSO组MMP-2及TIMP-2表达的吸光度(A)值的总体比较差异均有统计学意义(F=28.70,F=22.30,P<0.01)。MMP-2、TIMP-2的表达Lat-B组与BSS组比较差异有统计学意义(P<0.01),与DMSO组比较二者的表达均降低,差异均有统计学意义(P<0.01);BSS组和DMSO组间MMP-2及TIMP-2比较差异均无统计学意义(P>0.05)。结论 Lat-B能够有效降低眼压,明显提高巩膜的房水流出易度,并可通过上调MMP-2、TIMP-2的表达导致巩膜胶原重塑。Background Numerous studies have shown that the agents that alter cytoskeletal function in trabecular meshwork cells cen increase outflow facility.The agents,witch directly or indirectly disrupt F-actin,such as H-7,the latrunculins,and the cytochalasins,are particularly efficacious.Among the latrunculins,latrunculin（Lat）-B has been extensively tested for its effects on outflow facility.ObjectivePresent study was to investigate the effects of latrunculin（Lat-B）on intraocular pressure（IOP）and explore the permeability of sclera tissue to Lat-B.MethodsThirty-six dometic rabbits were divided into BSS group,DMSO group,Lat-B group.Lat-B,BSS,DMSO was topically administered to the lateral eye of each rabbit respectively in three groups.IOP was measured by Goldmann tonometer at 1 hour before administration of Lat-B and 1 hour,2,3,4,5,6,24 hours after administration of Lat-B respectively.All animals were sacrificed and the sclera tissue was obtained 24 hours later.Scleral permeability of BSS was detected by simulated filtration system,and the expression of matrix metalloproteinase-2（MMP-2）and tissue inhibitory metalloproteinase-2（TIMP-2）in the anterior sclera tissue was evaluated by using immunohistochemstry.This experiments adhered to Animal Protection Ordinance issued by the National Science Council in 1988.ResultsThe IOP change was significantly different among Lat-B group,BSS group and DMSO group（Fgroup=25.76,P0.01）or various time following the experiment（Ftime=4.50,P0.01）.The IOP of rabbit eye was significantly declined from 1 hour through 24 hours after administration of Lat-B in comparison with that of before use of drug（P0.01）,but no evidently differences of IOP were found between BSS group and DMSO group before and after experiment（P0.05）.Compared with BSS group and DMSO group,the filtration rate of Lat-B group via sclera was increased（P0.05）.Considerably difference was detected in the filtration of sclera tissue to drugs among Lat-B group,BSS group and DMSO group（Fgroup=47

关 键 词：latrunculin-B 眼压 细胞骨架重塑 基质金属蛋白酶 组织金属蛋白酶-2抑制剂 

分 类 号：R775[医药卫生—眼科]