[NIX-mediated mitochondrial autophagy in pathogenesis of myelodysplastic syndrome anemia].

• DOI: 10.3760/cma.j.issn.0376-2491.2017.14.009
• Publication Date: 2017-04-11
• Authors: Liyan Yang; Ningbo Cui; H Q Wang; Rong Fu; Weijie Qu; Er-Bao Ruan; X M Wang; G J Wang; Yahong Wu; H Liu; Song Jiang; Jian‐Long Guan; Lu Xing; L J Li; Huijuan Jiang; Yuhai Wang; C Y Liu; W Zhang; Zhenfa Shao
• Keywords: Pathogenesis

Objective: To investigate the change of NIX level bone marrow nucleated red blood cells in anemia patients with myelodysplastic syndromes (MDS), to explore significance NIX-mediated mitochondrial autophagy pathogenesis MDS anemia. Methods: A total 54 diagnosed Department Hematology General Hospital, Tianjin Medical University from July 2015 2016 were enrolled into group, 33 cases immune thrombocytopenia or idiopathic leukopenia as controls.The NIX, number mitochondria, membrane potential, reactive oxygen species (ROS) GlycoA(+) measured by flow cytometry; mRNA was PCR. Results: (1) The expression high-risk (0.61±0.24) significantly lower than that controls (0.79±0.16, P=0.027), and low-risk (0.81±0.15, P=0.011), while there no significant difference between patients. group (0.36±0.09) (1.44±0.41, P=0.027) (1.02±0.22, P=0.012); group. (2) mitochondria (937.17±707.85) higher (513.49±372.33, P=0.019) (461.74±438.02, P=0.008); controls. (3) potential (0.33±0.18) (0.61±0.32, P=0.001) (0.61±0.34, P=0.001); (4)The ROS (438.65±322.83) (242.77±136.87, P=0.006), (197.40±95.07, different (5) cell positively correlated percentage ring sideroblast (r=0.457, P=0.028) patients.(6) negatively concentration hemoglobin (r=-0.521, P=0.009) patients, but not Conclusion: is reduced which leads impaired autophagy, increased damaged apoptosis cells, thus related anemia.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患者有核红细胞线粒体数量与血红蛋白浓度呈负相关(r＝－0.521，P＝0.009)；低危组MDS患者有核红细胞线粒体数量与血红蛋白浓度无相关关系。结论：高危MDS患者有核红细胞NIX水平下降，线粒体自噬缺陷，线粒体清除障碍，有核红细胞凋亡增加，与贫血相关。.