本文選題：骨髓增生異常綜合征 + 地西他濱�。� 參考：《中國實驗血液學(xué)雜志》2017年05期

【摘要】：目的:探討去甲基化藥物地西他濱(Decitabine,DAC)的不同劑量對MDS-RAEB(骨髓增生異常綜合征-原始細胞增多型)細胞株MDS-L細胞增殖的抑制作用及其相關(guān)作用機制。方法:采用LC-MS/MS生物分析法檢測應(yīng)用DAC 20和15 mg/m~2×5 d的兩組MDS患者血藥濃度水平;模擬患者的血藥濃度,設(shè)計不同劑量的DAC(0.5、0.3、0.2、0.1、0.05、0.025和0.01μg/ml)作用于MDS-L細胞24、48、72和96 h,用CCK-8法檢測細胞的增殖抑制效應(yīng);光學(xué)顯微鏡下觀察細胞形態(tài)學(xué)變化;流式細胞術(shù)檢測細胞周期變化及凋亡情況;PCR檢測DAC作用后MDS-L細胞P15的甲基化水平的變化。結(jié)果:注射結(jié)束即刻,DAC 20 mg/m~2×5 d組患者血藥濃度為174.08±80.15(84.7-311)ng/ml,明顯高于15 mg/m~2×5 d組的89.87±32.94(43.2-165)ng/ml(P=0.014)。DAC對MDS-L細胞有明顯增殖抑制作用,且呈時間濃度依賴關(guān)系(r=0.786),但DAC≥0.1μg/ml濃度時,各濃度對細胞的抑制作用無明顯差異。DAC處理后G_1期細胞明顯增多,而S期細胞明顯減少。與對照組相比,MDS-L細胞經(jīng)DAC 0.01、0.025、0.05、0.1、0.2μg/ml作用96 h后,P15INK4B表達均下降,但各濃度之間無顯著差異(P0.05)。結(jié)論:低濃度DAC對MDS-L細胞有明顯增殖抑制作用,在0.1和0.2μg/ml濃度時,對MDS-L細胞的抑制作用達理想范圍。DAC可以將MDS-L細胞阻滯在G_1期,阻止G_1期細胞向S期細胞轉(zhuǎn)化。
[Abstract]:Aim: to investigate the inhibitory effects of different doses of the demethylated drug Decitabine DACon on the proliferation of MDS-RAEBcell line MDS-L cells and its related mechanism. Methods: LC-MS/MS bioassay was used to detect the serum drug concentration of MDS patients who were treated with DAC 20 and 15 mg/m~2 脳 5 d. MDS-L cells were treated with different doses of Dacron (0.5g / ml, 0.3g / ml and 0.025 渭 g / ml) for 2448g / ml for 72 h and 96 h, respectively. The proliferation inhibition effect was detected by CCK-8 assay, and the morphological changes were observed under optical microscope. The changes of cell cycle and apoptosis were detected by flow cytometry. The methylation level of P15 in MDS-L cells was detected by DAC. Results: the plasma drug concentration was 174.08 鹵80.15 渭 g/ml 84.7-311ng / ml in the 20 mg/m~2 脳 5 d group, which was significantly higher than that in the 15 mg/m~2 脳 5 d group (89.87 鹵32.94(43.2-165)ng/ml(P=0.014).DAC), in a time-dependent manner, but when DAC 鈮，

本文編號：1939347