Zhong Shan, Yang Guohua, Xia Cong, Duanlian Zhang, Shan Shengguo
Basic Medical School, Wuhan University, Wuhan, 430071, China.
J Huazhong Univ Sci Technolog Med Sci. 2009 Oct;29(5):614-9. doi: 10.1007/s11596-009-0516-3. Epub 2009 Oct 11.
The action mechanism of matrix metalloproteinases-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in the genesis, development and degeneration of haemangioma was investigated by detecting their expression in the tissue of haemangioma in different phases by using the immunohistochemistry. Fifty paraffin-embedded specimens of skin capillary haemangioma were collected, which were documented in the Department of Pathology, Renmin Hospital of Wuhan University from 2000 to 2006. All samples were stained by regular HE method, and proliferative cell nuclear antigen (PCNA) was tested by immunohistochemical S-P method. The samples were classified according to the Mulliken criteria and the expression pattern of PCNA. Immunohistochemical S-P method was applied to detect the expression of MMP-2 and TIMP-2 in proliferative and degenerative phases of cutaneous capillary haemangioma, and in normal skin tissues. In combination with the detection of the expression of factor VIII-related antigen, it was verified that in haemangioma tissues, the cells expressing MMP-2 and TIMP-2 were vascular endothelial cells. The MMP-2 and TIMP-2 expression was quantitatively analyzed by image analysis system (HPIAS-1000), and one-way ANOVA(107) and SNK(q) test were done to analyze average absorbance (A) and positive area rate of immunohistochemically positive particles by using SPSS11.5. The results showed: (1) Among 50 samples of haemangioma, there were 26 proliferative haemangiomas, and 24 degenerative haemangiomas, respectively; (2) The expression of MMP-2 was weak in normal vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression of MMP-2 in proliferative group was significantly higher than in degenerative group and control group (normal skin) (P<0.05), but there was no statistically significant difference between the latter two groups; (3) TIMP-2 was highly expressed in normal tissues, degenerative vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression level of TIMP-2 in proliferative phase was significantly lower than in degenerative phase (P<0.05), and the expression of TIMP-2 in proliferative phase was significantly different from that in degenerative phase and normal tissues (P<0.05). It was concluded that in proliferative phase of haemangioma, MMP-2 may promote over-proliferation of endothelial cells of haemangioma, and in degenerative phase, TIMP-2 can inhibit the proliferation of endothelial cells of haemangioma. The two substances play important roles in the genesis, development and degeneration of haemangiomas.
采用免疫组织化学方法检测基质金属蛋白酶-2（MMP-2）和金属蛋白酶组织抑制剂-2（TIMP-2）在不同时期血管瘤组织中的表达，以探讨其在血管瘤发生、发展及消退过程中的作用机制。收集武汉大学人民医院病理科2000年至2006年存档的50例皮肤毛细血管瘤石蜡包埋标本。所有标本均行常规HE染色，采用免疫组织化学S-P法检测增殖细胞核抗原（PCNA）。根据Mulliken标准及PCNA表达模式对标本进行分类。应用免疫组织化学S-P法检测皮肤毛细血管瘤增殖期和消退期以及正常皮肤组织中MMP-2和TIMP-2的表达。结合检测VIII因子相关抗原的表达，证实血管瘤组织中表达MMP-2和TIMP-2的细胞为血管内皮细胞。采用图像分析系统（HPIAS-1000）对MMP-2和TIMP-2表达进行定量分析，应用SPSS11.5软件进行单因素方差分析（One-way ANOVA）及SNK（q）检验，分析免疫组化阳性颗粒的平均吸光度（A）及阳性面积率。结果显示：（1）50例血管瘤标本中，增殖期血管瘤26例，消退期血管瘤24例；（2）正常血管内皮细胞、血管周围结缔组织细胞质及细胞外基质中MMP-2表达较弱。增殖期组MMP-2表达明显高于消退期组和对照组（正常皮肤）（P<0.05），而后两组间差异无统计学意义；（3）TIMP-2在正常组织、消退期血管内皮细胞、血管周围结缔组织细胞质及细胞外基质中高表达。增殖期TIMP-2表达水平明显低于消退期（P<0.05），增殖期TIMP-2表达与消退期及正常组织相比差异有统计学意义（P<0.05）。结论：在血管瘤增殖期，MMP-2可能促进血管瘤内皮细胞过度增殖，而在消退期，TIMP-2可抑制血管瘤内皮细胞增殖。这两种物质在血管瘤的发生、发展及消退过程中起重要作用。
