Ma Jie, Ji Linhua, Li Zhanquan, Liu Huihui, Zhao Chengyu, Xiong Hua, Wang Shengyan, Ge Ri-Li, Cui Sen
Department of Hematology, Affiliated Hospital of Qinghai University, Xining, China; Research Center for High Altitude Medicine, Qinghai University, Xining, China.
Department of Hematology, Affiliated Hospital of Qinghai University, Xining, China.
Blood Cells Mol Dis. 2019 May;76:25-31. doi: 10.1016/j.bcmd.2019.01.002. Epub 2019 Jan 9.
Chronic mountain sickness (CMS) has a higher incidence in the plateau region and is characterized by excessive erythrocytosis and hypoxemia. Bcl-2 family plays an important role in the process of erythropoiesis and the regulation of apoptosis. This study aimed to examine the change in apoptosis of erythroblasts in CMS patients and explore the involvement of Bcl-2 family. Bone marrow mononuclear cells (BMMNCs) were isolated by density gradient centrifugation from 18 CMS patients and 17 control participants. The apoptotic rate, mitochondrial membrane potential (MMP), the protein expression of caspase-3, TNFR, Fas, Bcl-2, Bax and Cyt-C were examined by flow cytometry, and mRNA expression was determined by real-time PCR. The results showed that apoptotic rate of erythroblasts was lower and MMP was higher in CMS group than in control group. The mRNA and protein expression levels of Bcl-2 were higher while Bax level was lower in CMS group than in control group. In CMS group, the apoptosis rate of CD71 erythroblasts was negatively correlated with the ratio of CD71 cells in BMMNCs and positively correlated with hemoglobin level. In conclusion, erythroblasts apoptosis is decreased due to the regulation of the expression of Bcl-2 family members in the erythroblasts of CMS patients.
慢性高山病（CMS）在高原地区发病率较高，其特征为红细胞增多和低氧血症。Bcl-2家族在红细胞生成和细胞凋亡调控过程中发挥重要作用。本研究旨在检测CMS患者成红细胞凋亡的变化，并探讨Bcl-2家族的参与情况。通过密度梯度离心法从18例CMS患者和17例对照者中分离出骨髓单个核细胞（BMMNCs）。采用流式细胞术检测凋亡率、线粒体膜电位（MMP）、半胱天冬酶-3、肿瘤坏死因子受体（TNFR）、Fas、Bcl-2、Bax和细胞色素C（Cyt-C）的蛋白表达，通过实时聚合酶链反应测定mRNA表达。结果显示，CMS组成红细胞凋亡率低于对照组，MMP高于对照组。CMS组Bcl-2的mRNA和蛋白表达水平高于对照组，而Bax水平低于对照组。在CMS组中，CD71成红细胞的凋亡率与BMMNCs中CD71细胞的比例呈负相关，与血红蛋白水平呈正相关。总之，由于CMS患者成红细胞中Bcl-2家族成员表达的调控，成红细胞凋亡减少。
