骨髓增生异常综合征患者有核红细胞自噬水平的研究  

Study on autophagy in nucleated red blood cells in patients with myelodysplastic syndromes

作　　者：杨丽艳[1] 王化泉[1] 付蓉[1] 瞿文[1] 阮二宝[1] 王晓明[1] 王国锦[1] 吴玉红[1] 刘鸿[1] 宋嘉[1] 关晶[1] 邢莉民[1] 李丽娟[1] 江汇涓[1] 刘惠[1] 王一浩[1] 刘春燕[1] 张薇[1] 邵宗鸿[1] 

机构地区：[1]天津医科大学总医院血液科,300052

出　　处：《中华血液学杂志》2017年第5期432-436,共5页Chinese Journal of Hematology

基　　金：国家自然科学基金（81170472、81400088）;天津市应用基础与前沿技术研究计划（14JCYBJC27200、09JCYBJC11200）;天津市抗癌重大专项攻关计划（12ZCDZSY17900）

摘　　要：目的研究骨髓增生异常综合征（MDS）患者有核红细胞的自噬水平。方法54例MDS患者为实验组，对照组33例。采用透射电镜观察自噬过程，流式细胞术检测骨髓细胞中GlycoA＋有核红细胞自噬相关蛋白微管相关蛋白轻链3B（LC3B）的表达水平，Real-time PCR法检测GlycoA＋有核红细胞自噬相关基因AMPK、ULK1和mTOR mRNA的表达，Western blot法检测GlycoA＋有核红细胞线粒体外膜蛋白TOM20的表达。结果MDS患者有核红细胞中不易观察到自噬体及自噬溶酶体。相对高危组MDS患者有核红细胞LC3B表达（0.22±0.12）显著低于对照组（0.43±0.22，P〈0.001）及相对低危组（0.40±0.16，P=0.001）。相对高危组患者AMPK、ULK1 mRNA表达水平明显低于对照组[AMPK：0.26（0.60）对1.00（2.07），ULK1：0.27（3.31）对1.07（4.41），P值均〈0.017]，mTOR mRNA表达水平明显高于对照组[1.82（3.74）对1.26（1.38），P〈0.017]。相对高危组MDS患者有核红细胞LC3B水平与HGB呈正相关（r=0.529，P=0.009）。相对高危组MDS患者有核红细胞TOM20蛋白（9.42±4.42）表达升高。结论高危MDS患者有核红细胞自噬水平下降。ObjectiveTo investigate the change of autophagy level of bone marrow nucleated red blood cell （RBC） in patients with myelodysplastic syndromes （MDS） .MethodsFifty-four MDS patients and thirty-three controls were enrolled in this study. The mitophagy were observed by transmission electron microscopy （TEM） . The level of autophagy-associated protein LC3B in GlycoA＋ nucleated RBC was measured by flow cytometry. The expressions of ULK1 and mTOR mRNA in GlycoA＋ nucleated RBC were measured by real-time PCR. The expression of the mitochondrial outer membrane protein TOM20 in GlycoA＋ nucleated RBC was detected by Western blot.ResultsAutophagosomes or autolysosomes were scarcely observed by TEM in MDS patients. The expression of LC3B in GlycoA＋ nucleated RBC in high-risk MDS patients （0.22±0.12） was significantly lower than that in normal controls （0.43±0.22, P〈0.001） , and lower than that in low-risk MDS patients （0.40±0.16, P=0.001） . The expression of AMPK [0.26 （0.60） ] in GlycoA＋ nucleated RBC in high-risk MDS patients was significantly lower than that in controls [1.00 （2.07） , P〈0.017） . The expression of ULK1 mRNA in GlycoA＋ nucleated RBC in high-risk MDS patients [0.27 （3.31） ] was significantly lower than that in controls [1.07 （4.41） , P〈0.017]. The level of mTOR mRNA in GlycoA＋ nucleated RBC in high-risk MDS patients [1.82 （3.74） ] was significantly higher than that in controls [1.26 （1.38） , P〈0.017]. The level of LC3B in GlycoA＋ nucleated RBC was negatively correlated with the HGB （r=0.529, P=0.009） in high-risk MDS patients. The expression of mitochondrial outer membrane protein TOM20 in high-risk MDS patients was 9.42±4.42.ConclusionAutophagy is impaired in nucleated RBC of MDS patients.

关 键 词：骨髓增生异常综合征 自噬 贫血 

分 类 号：R551.3[医药卫生—血液循环系统疾病]