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本研究主要探讨骨髓增生异常综合征(MDS)及白血病患者中基质细胞衍生因子-1(SDF-1)在细胞凋亡、迁移和黏附中的作用及相关的信号转导。选取37例初发MDS患者〔低危组(IPSS≤1.0)22例,高危组(IPSS≥1.5)15例〕、10例初发白血病患者及14例良性贫血患者(作为对照组),通过流式细胞术检测骨髓CD34+细胞表面CXCR4的表达水平及CD34+细胞的凋亡情况。选取4例低危MDS患者和5例高危MDS患者,通过微孔细胞迁移实验检测SDF-1对细胞的趋化作用。通过CCK-8法检测SDF-1对细胞之间黏附能力的影响。结果表明,低危MDS组骨髓内CD34+细胞的凋亡率明显高于高危MDS组(21.33%vs 7.27%,p<0.001),同样低危MDS组骨髓内CD34+细胞的凋亡率明显高于白血病组(21.33%vs 7.53%,p<0.001),未发现CD34+细胞的凋亡率与患者年龄性别有相关性。SDF-1能够促进高表达CXCR4患者的细胞黏附于基质细胞并能诱导该细胞的迁移,诱导细胞形态发生极化,上述作用可以被G蛋白抑制剂pertussis toxin、PI3K抑制剂wortmannin及CXCR4拮抗剂AMD3100明显抑制;而对低表达CXCR4的患者细胞则无上述抑制作用。结论:SDF-1/CXCR4通过PI3K信号通路提高细胞的迁移及黏附能力,发挥抗凋亡作用,上述作用可以被PI3K途径抑制剂和G蛋白抑制剂所阻断。
The aim of this study was to investigate the role of SDF-1 in apoptosis, migration and adhesion in patients with myelodysplastic syndrome (MDS) and leukemia and its related signal transduction. Thirty-seven patients with newly diagnosed MDS (22 in low-risk group (IPSS≤1.0), 15 in high-risk group (IPSS≥1.5), 10 patients with primary leukemia and 14 patients with benign anemia (control group) Cytometry was used to detect the expression of CXCR4 on CD34 + cells and the apoptosis of CD34 + cells. Four patients with low-risk MDS and five patients with high-risk MDS were selected and the chemotactic effect of SDF-1 on cells was detected by microporous cell migration assay. The effect of SDF-1 on cell adhesion was examined by CCK-8 assay. The results showed that the apoptosis rate of CD34 + cells in the low-risk MDS group was significantly higher than that in the high-risk MDS group (21.33% vs 7.27%, p <0.001). Similarly, the apoptosis rate of the CD34 + cells in the low-risk MDS group was significantly higher than that in the leukemia Group (21.33% vs 7.53%, p <0.001). No correlation was found between the apoptotic rates of CD34 + cells and age and sex of the patients. SDF-1 can promote the adhesion of cells with high expression of CXCR4 to stromal cells and induce the migration of cells and induce the polarization of cell morphology. These effects can be blocked by G protein inhibitor pertussis toxin, PI3K inhibitor wortmannin and CXCR4 antagonist AMD3100 Significantly inhibited; while low expression of CXCR4 cells in patients without the above inhibition. Conclusion: SDF-1 / CXCR4 can enhance cell migration and adhesion through the PI3K signaling pathway and exert anti-apoptotic effects. These effects can be blocked by PI3K pathway inhibitors and G-protein inhibitors.