MMP-9／TIMP-1表达失衡与糖尿病大鼠皮肤“隐性损害”关系的初步探讨  

Imbalance of MMP-9/TIMP-1 during the cutaneous ＂underlying disorder＂ in diabetic rats

作　　者：严励[1] 朱平[1] 陈黎红[1] 杨川[1] 劳国娟[1] 杜婧[1] 郝少云[1] 程桦[1] 

机构地区：[1]中山大学附属第二医院内分泌代谢科,广州510080

出　　处：《中华内分泌代谢杂志》2008年第5期533-536,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：卫生部临床学科重点项目（编号卫规财发[2004]468号）;广东省自然科学基金资助项目（编号2005-311-05001711）

摘　　要：目的观察基质金属蛋白酶9（MMP-9）、组织金属蛋白酶抑制物1（TIMP-1）的表达和MMP-9／TIMP-1比值在糖尿病组和正常组大鼠皮肤表达的变化，并探讨其可能的作用。方法采用链脲佐菌素制备糖尿病大鼠模型，6周后采用HE染色、免疫组织化学方法评估皮肤组织的组织学、细胞生物学行为的情况；通过逆转录-聚合酶链反应（RT-PCR）和Western印迹检测两组大鼠皮肤MMP-9、TIMP-1的表达情况。结果与对照组比较，糖尿病组皮肤表皮厚度变薄，皮肤组织层次欠清晰、缺乏复层排列、明显萎缩，真皮纤维束排列紊乱、纤维间距增加、炎性细胞浸润。糖尿病组皮肤MMP-9的表达高于正常组，而TIMP-1的表达低于正常组，MMP-9／TIMP．1蛋白水平比值高于正常组。结论糖尿病鼠皮肤在组织结构完整性未遭到破坏的情况下已经存在组织学、细胞生物学行为的改变，这种“隐性损害”可能与MMP-9／TIMP-1的平衡改变有关。Objective To investigate the change of matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （ TIMP-1 ） in the skin of diabetic rats, and to explore the potential role of MMP-9/ TIMP-1. Methods Diabetic rats were induced with streptozotocin （STZ）. Then all rats were maintained for 6 weeks. Routine pathological examination and immunohistochemistry were made to reveal the histological and cytological appearances. RT-PCR and Western blotting were used to detect the expression of mRNA and protein of MMP-9 and TIMP-1 in the skin. Results Six weeks after STZ treatment, examination of HE-stained skin sections from normal and diabetic animals revealed that the epidermis and dermis layers were thinner in diabetic rats than those in control rats. The skin of diabetic rats showed features of atrophy such as disorganization of connective tissue fiber bundles and enlarged space between collagen fiber bundles. In contrast, thick bundles of connective tissue were observed in the dermis of normal rat skin. In normal skin, cells had a bipolar, spindle-shaped appearance in the thick collagen bundles, while in the skin of diabetic animals the interstitial cells had a rounded, shrunken and crenated appearance. The relative values of expression of MMP-9 in diabetic group were higher than those in normal group with significant difference, however, the relative values of expression of TIMP-1 in diabetic group were lower than those in control group. Conclusion The changes in cutaneous histology and cytology appear earlier than skin wound. These ＂underlying disorders＂ may be associated with the imbalance of MMP-9/TIMP-1.

关 键 词：糖尿病 皮肤组织 基质金属蛋白酶 组织金属蛋白酶抑制剂 

分 类 号：R587.2[医药卫生—内分泌]