慢性高原病患者骨髓单个核细胞Bcl-2、Bcl-xl、Bax及Bid蛋白水平表达研究

发布时间：2018-06-02 03:21

本文选题：慢性高原病 + Bcl-2家族蛋白　；参考：《青海大学》2015年硕士论文

【摘要】：目的:慢性高原病(CMS)是高原地区常见病,主要特征之一是红细胞过度积累,但其机制尚未完全阐明。细胞凋亡机制在生理造血调控中发挥着重要的作用。我们的前期研究发现CMS造血细胞凋亡下调。本文旨在研究细胞凋亡调节蛋白Bcl-2、Bcl-xl、Bax及Bid在慢性高原病(CMS)骨髓单个核细胞(BMMNCs)的变化及与血清EPO等临床指标的相关性,探讨其在红细胞积累中的可能作用。方法:CMS组以按照第六届国际高原医学和低氧生理学术大会诊断标准诊断的20例CMS患者为研究对象,平均年龄(49.45±9.94)岁,均为男性,汉族,世居于海拔2500米以上,且排除其他因素引起的红细胞增多症;对照组为同海拔地区世居健康体检者20例,平均年龄(47.9±12.84)岁,均为男性,汉族,排除心、肺、肝、肾疾患。行骨髓穿刺采集研究对象骨髓液,应用Western blot方法检测20例CMS患者及20例健康者BMMNCs Bcl-2、Bcl-xl、Bax及Bid蛋白水平;采集外周静脉血清,应用ELISA法测定血清EPO水平,并进行比较分析Bcl-2、Bcl-xl、Bax、Bid及EPO与CMS主要临床、实验室指标的相关性。结果:(1)CMS患者BMMNCs Bid蛋白表达水平高于对照组(0.59±0.40 vs.0.36±0.27,P=0.037);(2)两组间BMMNCs Bcl-2蛋白表达水平未发现统计学差异([0.0097(0.00,0.45)vs.0.0514(0.00,0.51)],Z=-0.56,P=0.57);(3)CMS患者BMMNCs Bax蛋白表达水平为0.78±0.50,对照组为0.73±0.50,两组间亦未发现统计学差异(P=0.75);(4)CMS患者及对照组BMMNCs均未检测到Bcl-xl蛋白表达;(5)CMS组外周血EPO水平[(269.28±127.77)pg/ml]明显高于对照组[(131.31±67.65)pg/ml],P=0.004。(6)CMS患者Hb、EPO分别与Bcl-2、Bax、Bid蛋白间均未发现明显相关性(P0.05)。结论:CMS骨髓单个核细胞Bcl-2家族分子Bid蛋白高表达,但与Hb无相关性,而Bcl-2、Bax蛋白水平与同海拔健康者间无差异,与Hb亦无相关性,提示CMS造血细胞Bcl-2家族分子有一定程度的异常;CMS患者血清EPO水平较同一海拔健康人升高。CMS造血凋亡异常的机制需要进一步研究。
[Abstract]:Objective: chronic high altitude disease (CMS) is a common disease in highland area, one of the main characteristics is erythrocyte excessive accumulation, but its mechanism has not been fully elucidated. Apoptosis plays an important role in the regulation of physiological hematopoiesis. Our previous study found that CMS hematopoietic cell apoptosis was down-regulated. The purpose of this study was to investigate the changes of apoptosis regulatory protein Bcl-2Bcl-xlCsin bone marrow mononuclear cells (BMMNCs) of chronic high altitude disease (CMSs) and the relationship between BMMNCsand serum EPO, so as to explore the possible role of BMMNCsin erythrocyte accumulation. Methods Twenty patients with CMS diagnosed in accordance with the diagnostic criteria of the sixth International Conference on altitude Medicine and hypoxic Physiology were studied. The mean age of 20 CMS patients was 49.45 卤9.94 years old. All of them were male and Han nationality, who lived above 2500 meters above sea level. In the control group, 20 healthy persons (mean age 47.9 卤12.84) years old, male, Han nationality, excluding heart, lung, liver and kidney diseases were found in the control group. Bone marrow fluid was collected by bone marrow puncture. The levels of BMMNCs Bcl-2Bcl-xlPBax and Bid protein were detected by Western blot method in 20 patients with CMS and 20 healthy subjects, and the serum EPO levels were measured by ELISA method, and the peripheral venous blood samples were collected. The correlation between the clinical and laboratory indexes of Bcl-2P Bcl-XL Bax-Bid, EPO and CMS was compared and analyzed. Results there was no significant difference in the expression of BMMNCs Bid protein between the two groups (0. 59 卤0. 40 卤0. 27 vs.0.36 卤0. 27 vs.0.36 卤0. 037). There was no statistical difference between the two groups ([0. 0097 0. 0. 45 Vs.0.0514. 0. 001)] the expression level of BMMNCs Bax protein was 0. 78 卤0. 50, 0. 78 卤0. 50, and 0. 73 卤0. 50 in the control group, respectively. There was no statistical difference between the two groups in the expression of BMMNCs Bax protein. There was no significant correlation between the expression of Bcl-xl protein and the protein of Bcl-2Bax-Bid in BMMNCs of patients and controls. The level of EPO in peripheral blood [269.28 卤127.77)pg/ml] was significantly higher than that in control group (131.31 卤67.65)pg/ml). Conclusion the expression of Bid protein in Bcl-2 family of bone marrow mononuclear cells is high, but there is no correlation with HB, but there is no difference between Bcl-2nBax protein level and healthy individuals at the same altitude, nor is there any correlation between Bcl-2nBax protein and HB. It is suggested that the level of serum EPO in patients with CMS hematopoietic cells with abnormal Bcl-2 family molecules is higher than that in healthy persons at the same altitude. The mechanism of abnormal hematopoietic apoptosis in patients with CMS hematopoietic cells needs to be further studied.
【学位授予单位】：青海大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R594.3

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