摘要
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。
AIM: To explore the role of MMP-2, MMP-9 and TIMP-2 in the development of DRP.· METHODS: Immunohistochemical technique and computer image-analysing instrument were used to analyse the expression of MMP-2,MMP-9 and TIMP-2 in the retinae of C57BL/KsJ db/db diabetic mice, their thin db/+ litters being normal controls.SAS was used to analyse the data.· RESULTS: As diabetes duration progressed, the retinal microvascular basement membrane of diabetic mice were thickened; The expression of MMP-2 and MMP-9 in the retinae of diabetic mice decreased significantly (P < 0.05); The expression of TIMP-2 increased significantly (P <0.05); The ratio of MMP-2/TIMP-2 at the same duration decreased significantly (P <0.05).· CONCLUSION: As diabetes duration progressed,the activation of MMP-2 are naturally inhibited by the 1:1 compound formation of MMP-2 and TIMP-2 due to the high level of TIMP-2. Moreover,the expression of MMP-9 decreased significantly. These may lead to the gradually thickened retinal microvascular basement membrane in the early DRP.·
出处
《国际眼科杂志》
CAS
2004年第4期610-614,共5页
International Eye Science
关键词
基质金属蛋白酶
组织抑制剂
糖尿病
小鼠
视网膜组织
表达
matrix metalloproteinase-2 (MMP-2)
matrix metalloproeinase-9(MMP-9)
tissue inhibitor of metalloproteinase-2(TIMP-2)
diabetic-retinopathy(DRP)
immunohistochemistry
