急性髓系白血病82例患者VEGF与MMP-2、MMP-9的相关性研究

Relationship between VEGF and MMP-2, MMP-9 in 82 Patients with Acute Myeloid Leukemia

为了探讨急性髓系白血病(AML)患者中血管内皮生长因子(VEGF)与基质金属蛋白酶MMP-2、MMP-9的相互关系及二者在AML中的意义,采用半定量RT-PCR技术检测AML患者与正常人骨髓单个核细胞(MNC)MMP-2mRNA、MMP-9mRNA、VEGF mRNA的表达,用明胶酶谱的方法测定原代MNC和HL-60细胞分泌的MMP-2、MMP-9的活性,应用ELISA方法检测AML患者血清中VEGF蛋白的水平,分析VEGF和MMP-2、MMP-9mRNA之间的关系。结果显示:AML患者MMP-2mRNA、MMP-9mRNA与VEGF mRNA的表达和VEGF蛋白水平呈正相关,缓解期患者和正常对照无相关性;VEGF阳性组发生髓外浸润率明显高于阴性组;VEGF上调HL-60细胞中bcl-2的表达。结论:AML患者中MMP-2,MMP-9的表达和VEGF具有正相关性,VEGF可以上调部分AML患者中MMP-2,MMP-9的表达,VEGF可能与MMP-2,MMP-9共同参与了白血病髓外浸润的发生。

In order to investigate the relationship between VEGF and matrix metalloproteinase （MMP）-2, -9 in acute myeloid leukemia patients, and evaluate the significance of them in extramedullary leukemic invasion, the expressions of MMP-2 mRNA, MMP-9 mRNA, VEGF mRNA in bone marrow from 86 patients with acute myeloid leukemia （ AML）, as well as human hematopoietic cell lines were analyzed by reverse transcription-polymerase chain reaction （RT-PCR）. The proteolytic activities of MMP-2 and MMP-9 in the supernatants were measured by zymography. The VEGF protein in serum of all samples was detected by ELISA. All these results were analyzed for determination of the relationship between VEGF and MMP-2, MMP-9. The results showed that there was a positive correlation between expressions of MMP-2 mRNA or MMP-9 mRNA and VEGF mRNA or protein. But no such correlation was demonstrated in the AML （CR） and normal control （NC） groups. A higher expression level of MMP-2 and MMP-9 in the VEGF positive group was found, as compared with the negative group （ P 〈 0.05 ）. More extramedullary infiltration occured in VEGF positive groups than that in VEGF negative groups of AML. The expression of bcl-2 in HL-60 cells was upregulated by VEGF. It is concluded that there are significantly positive correlations between the expression of MMP-2 and MMP-9 with VEGF mRNA or protein levels in AML patients. VEGF can upregulate the expression of MMP-2, MMP-9 in HL-60 and a part of the primary leukemic cells. VEGF and MMP-2, MMP-9 may participate in the extramedullary leukemic invasion of AML patients.