NIX介导线粒体自噬在骨髓增生异常综合征贫血发病机制中的作用  

NiX-mediated mitochondrial autophagy in pathogenesis of myelodysplastic syndrome anemia

作　　者：杨丽艳[1] 崔宁博[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：《中华医学杂志》2017年第14期1071-1075,共5页National Medical Journal of China

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）患者有核红细胞线粒体外膜蛋白NIX水平的变化，初步探讨NIX介导线粒体自噬在MDS贫血发病机制中的作用。 方法选取2015年7月至2016年7月天津医科大学总医院血液内科收治的54例MDS患者为实验组，并分为高危组和低危组；免疫性血小板减少症及特发性白细胞减少症患者33例为对照组。流式细胞术检测骨髓细胞中糖蛋白抗原A（GlycoA＋）有核红细胞NIX表达水平、线粒体数量、线粒体膜电位和氧自由基（ROS）水平；实时荧光定量PCR检测骨髓细胞中GlycoA＋有核红细胞NIX mRNA水平。 结果（1）流式结果显示高危组MDS患者有核红细胞NIX表达（0.61±0.24）显著低于对照组（0.79±0.16，P＝0.027），显著低于低危组（0.81±0.15，P＝0.011），低危组与对照组比较差异无统计学意义；PCR结果显示高危组MDS患者GlycoA＋有核红细胞NIX mRNA水平（0.36±0.09）显著低于对照组（1.44±0.41, P＝0.027） ，显著低于低危组（1.02±0.22, P＝0.012），低危组与对照组比较差异无统计学意义。（2）高危组MDS患者有核红细胞线粒体数量（平均荧光强度937.17±707.85）显著高于对照组（513.49±372.33，P＝0.019），显著高于低危组（461.74±438.02，P＝0.008），低危组与对照组比较差异无统计学意义。（3）高危组MDS患者有核红细胞线粒体膜电位水平（0.33±0.18）显著低于对照组（0.61±0.32，P＝0.001），显著低于低危组（0.61±0.34，P＝0.001）；低危组与对照组比较差异无统计学意义。（4）高危组MDS患者有核红细胞ROS水平（平均荧光强度438.65±322.83）显著高于对照组（242.77±136.87，P＝0.006），显著高于低危组（197.40±95.07，P＝0.001）,低危组与对照组比较差异无统计学意义。（5）MDS患者有核红细胞线粒体数量与环形铁粒幼细胞比例呈正相关（r＝0.457，P＝0.028）。（6）高危组MDS�Objective To investigate the change of NIX level of bone marrow nucleated red blood cells in anemia patients with myelodysplastic syndromes （MDS） , to explore the significance of NIX-mediated mitochondrial autophagy in the pathogenesis of MDS anemia. Methods A total of 54 patients with MDS diagnosed in the Department of Hematology of General Hospital, Tianjin Medical University from July 2015 to July 2016 were enrolled into the MDS group, 33 cases of immune thrombocytopenia or idiopathic leukopenia as controls. The level of NIX, the number of mitochondria, mitochondrial membrane potential,the level of reactive oxygen species （ROS） in GlycoA ~ nucleated red blood cells were measured by flow cytometry; the level of NIX mRNA was measured by PCR. Results （1） The expression of NIX in GlycoA ± nucleated red blood cells in high-risk MDS patients （0. 61 ± 0. 24） was significantly lower than that in controls （0. 79 ± 0. 16, P = O. 027 ）, and lower than that in low-risk MDS patients （0. 81 ±O. 15, P = 0. 011 ）, while there was no significant difference between the controls and low-risk MDS patients. The expression of NIX mRNA in GlycoA± nucleated red blood cells in high-risk MDS group （0. 36 ±. 09） was lower than that in the controls （ 1.44 ±0. 41, P =0. 027） and that in the low-risk group （ 1.02 ±0. 22, P = 0. 012） ; there was no significant difference between the controls and the low-risk group. （2） The number of mitochondria in GlycoA nucleated red blood cells in high-risk MDS patients （937.17 ± 707.85 ） was signiticantly higher than that in the controls （513.49 ±372. 33, P= 0. 019） and that in low-risk MDS patients （461.74 ±438.02 ,P = 0. 008 ）; while there was no significant difference between low-risk MDS patients and the controls. （3） The level of mitochondrial membrane potential in GlycoA nucleated red blood cells in high-risk MDS patients （0.33 ±0. 18） was significantly lower than that in the controls （0. 61 ± 0.32,P=0.001） and that in l

关 键 词：骨髓增生异常综合征 贫血 红细胞 线粒体 

分 类 号：R551.3[医药卫生—血液循环系统疾病]