基质金属蛋白酶-1及其抑制剂和转化生长因子-β1在糖尿病结膜松弛症结膜组织中的表达

Expression and significance of transforming growth factor-β1,matrix metalloproteinase-1 and its inhibitor in diabetic conjunctivochalasis

目的测定基质金属蛋白酶-1(MMP-1)及其抑制剂(TIMP-1)和转化生长因子-β1(TGF-β1)在糖尿病结膜松弛症患者结膜中的表达,探讨其在糖尿病结膜松弛症发生过程中的作用机制。方法按照张兴儒眼结膜松弛症临床分级标准和1999年WTO糖尿病诊断标准,经手术共收集待检结膜标本36份,其中包括糖尿病结膜松弛症6例9眼(糖尿病结膜松弛症组)、单纯结膜松弛症5例9眼(单纯结膜松弛症组)、糖尿病不伴结膜松弛症9例9眼(糖尿病组)和行白内障囊外摘出术(ECCE)手术的正常对照9例9眼(正常结膜组)。采用免疫组织化学SP法检测并比较各组结膜组织中MMP-1、TIMP-1和TGF-β1的表达。结果 MMP-1在糖尿病结膜松弛症和单纯结膜松弛症组患者结膜中阳性表达的平均吸光度(A)值分别为0.2732±0.0285和0.2599±0.0229,明显高于糖尿病组和正常结膜组的0.1872±0.0138和0.1485±0.0079,差异均有统计学意义(P<0.05);TIMP-1的表达在各组间差异无统计学意义(F=2.470,P=0.079)。TGF-β1在糖尿病结膜松弛症组患者结膜中的阳性表达高于单纯结膜松弛症组、糖尿病组和正常结膜组(0.2065±0.0331vs0.1866±0.0129;0.2065±0.0331vs0.1773±0.0153;0.2065±0.0331vs0.1632±0.0155),差异均有统计学意义(P<0.05)。结论 MMP-1和TIMP-1表达失衡在糖尿病结膜松弛症的发生发展过程中起重要作用,此过程不受TGF-β1的调控。

Background Conjunctivochalasis often lead to abnormality of ocular surface,but its machanism is still unclear.It has been found that conjunctivochalasis may occurred in diabetes patient.Objective This study was to investigate the expression and role of transforming growth factor β1,matrix metalloproteinase 1 and its inhibitor in diabetic conjunctivochalasis.Methods Thirty-six conjunctive tissue samples were collected during surgery from the patients with diabetic conjunctivochalasis （9 eyes of 6 cases）,only conjunctivochalasis （9 eyes of 5 cases）,diabetes without conjunctivochalasis （9 eyes of 9 cases） and normal subjects received extracapsular extraction （9 eyes of 9 cases）.The grouping was performed according to the clinical grading criteria of zhang and diagnostic criteria of diabetes by WHO （1997 version） Expressions of matrix metalloproteinase （MMP-1）,tissue inhibitor of metalloproteinase （TIMP-1） and transforming growth factor （TGF-β1） in conjunctiva tissue were detected by immunohistochemistry.Written informed consent was obtained from each patient prior to the medical initial.Results Immunohistochemistry revealed that the positive expressions of MMP-1,TIMP-I and TGF-β1 mainly located in cytoplasm and cellular membrane.Expressions of MMP-1 in conjunctival tissue （A value） in diabetic conjunctivochalasis and only conjunctivochalasis were 0.273 2±0.028 5 and 0.259 9±0.022 9,showing a stronger expression than those of diabetes group and normal conjunctiva group （0.187 2±0.013 8,0.148 5±0.007 9） （P〈0.05）.There was no statistically significant difference in the expression of TIMP-1 among 4 groups （F=2.470,P=0.079）.The positive expression of TGF-β1 in conjunctival tissue with diabetic conjunctivochalasis was stronger than that in diabetes mellitus group and normal conjunctiva group （0.186 6±0.012 9 vs 0.177 3±0.015 3,0.186 6±0.012 9 vs 0.163 2±0.015 5） （P〈0.05）.Conclusion The imbalance between the expression of MMP-1 and TIMP-1 may play a critical role during the development of diabetic conjunctivochalasis.This process is not regulated by TGF-β1.