慢性高原病患者骨髓组织Gas6及其受体表达水平研究

发布时间：2018-06-25 11:48

  本文选题：慢性高原病 + 红细胞增多　； 参考：《青海大学》2015年硕士论文

【摘要】：背景慢性高原病(chronic mountain sickness,CMS)是长期生活在海拔高度2500米以上地区的移居者或世居者,对高原低氧环境逐渐失去习服而发生的临床综合征,又称Monge病,曾称高原红细胞增多症(high altitude polycythemia,HAPC),以红细胞过度增生、低氧血症为特征,常伴有肺动脉高压。CMS红细胞过度积累的机制尚未阐明,研究提示存在非红细胞生成素(erythropoietin,EPO)依赖性调控机制。近年研究显示,造血组织、造血细胞和骨髓基质细胞表达Gas6蛋白和TAM受体的全部成员,提示Gas6-TAM受体参与造血调控。有资料证明,在前列腺癌组织中,Gas6、Axl受体与低氧诱导因子-1α共同表达,低氧强化Gas6-Axl受体的信号转导。由此可见,Gas6-TAM系统在红系造血中发挥调控作用,且可能受低氧的影响。我们结合CMS的病因和血液系统主要的病理生理特点,提出一个假设,CMS患者循环血液和/或骨髓组织/细胞中Gas6-TAM系统成分的表达水平和活性异常,异常的Gas6-TAM系统可能与红细胞增多有关,尤其骨髓局部Gas6以旁分泌/自分泌机制促进红细胞增生,导致红细胞增多。目的 测定HB、HCT等参数,采用ELISA法测定骨髓液和血液Gas6蛋白质水平;RT-PCR法检测骨髓单个核细胞Gas6、TAM受体(Tyro3,Axl和Mer)m RNA水平。必要时计算Gas6浓度的骨髓-血液梯度(骨髓液浓度减去血液浓度),并进行对比分析和相关性分析,分析CMS患者骨髓、外周血细胞Gas6及其TAM受体对红细胞增多的可能作用。方法 以CMS患者为20例为研究对象(研究组),以居住同一海拔高度地区3年以上的健康人20名为对照组。测定HB、HCT、Sa O2等参数,采用ELISA法测定骨髓液和血液Gas6蛋白质水平;RT-PCR法检测骨髓单个核细胞Gas6、TAM受体(Tyro3,Axl和Mer)m RNA表达水平。必要时计算Gas6的骨髓-血液梯度(骨髓液浓度减去血液浓度)。进行比较分析和相关指标之间的相关性分析。结果 ①骨髓Mer m RNA、Axl m RNA、Gas6 m RNA、骨髓及外周血Gas6蛋白表达水平:CMS骨髓Mer m RNA[0.39(0.31)%]表达水平低于对照组[0.97(0.92)%],差异有统计学意义(P0.05)。CMS组骨髓Axl m RNA[(0.39±0.45)%]、Gas6 m RNA[(0.44±0.36)%]与对照组[(0.64±0.55)%]、[(0.58±0.34)%]比较,差异无统计学意义(P0.05)。CMS骨髓Gas6蛋白[(35.64±9.12)pg/m L]与对照组骨髓Gas6蛋白[(38.94±5.99)pg/m L]比较,差异无统计学意义(P0.05)。CMS血液Gas6蛋白[(35.27±7.43)pg/m L]与对照组血液Gas6蛋白[(34.21±9.56)pg/m L]比较,差异无统计学意义(P0.05)。CMS骨髓Gas6蛋白[(35.64±9.12)pg/m L]与CMS血液Gas6蛋白[(35.27±7.43)pg/m L]比较,差异无统计学意义(P0.05)。对照组骨髓Gas6蛋白[(35.64±9.12)pg/m L]与对照组血液Gas6蛋白[(34.21±9.56)pg/m L]比较,差异无统计学意义(P0.05)。②CMS患者Sa O2、HB、HCT分别为(89.42±4.25)%、(224.75±16.15)g/L、(69.04±6.70)%,与对照组(96.86±0.78)%、(138.00±17.21)g/L、(39.90±2.24)%比较,差异有统计学意义(P0.05)。CMS患者年龄[(47.83±8.11)岁]与对照组[(47.33±14.21)岁]比较,差异无统计学意义(P0.05)。③各指标间相关性分析:CMS患者及对照组骨髓MNC中Gas6 m RNA、Axl m RNA、Mer m RNA表达水平及骨髓及血液Gas6蛋白表达水平与HB水平间均无相关性(均P0.05),且CMS患者及对照组骨髓MNC中Gas6 m RNA、Axl m RNA、Mer m RNA表达水平及骨髓及血液Gas6蛋白表达水平相互间亦无相关性(均P0.05)。结论 ①CMS组及健康对照组骨髓均表达Gas6及其受体Axl、Mer,但CMS组Mer m RNA表达水平较对照组降低。②CMS组及对照组骨髓及血液均表达Gas6,两组间Gas6蛋白表达水平无差异,且未发现骨髓局部Gas6存在旁分泌/自分泌机制。③CMS患者及对照组骨髓MNC中Gas6 m RNA、Axl m RNA、Mer m RNA、骨髓及血液Gas6蛋白表达水平与HB水平间均无相关性,且Gas6及其受体相互间亦无相关性。
[Abstract]:Background chronic plateau disease (chronic mountain sickness, CMS) is a long-term living or living person living at an altitude of more than 2500 meters above sea level. The clinical syndrome, also known as Monge disease, is called Monge disease (high altitude polycythemia, HAPC), and hyperproliferation of red blood cells. The mechanism of hypoxemia, which is often accompanied by excessive accumulation of.CMS red blood cells in pulmonary arterial hypertension, has not been elucidated. The study suggests the existence of non erythropoietin (erythropoietin, EPO) dependent regulatory mechanism. In recent years, all members of hematopoietic tissue, hematopoietic cells and bone marrow stromal cells express Gas6 protein and TAM receptor, suggesting Gas6-TAM The receptor is involved in the regulation of hematopoiesis. It is shown that in prostate cancer, Gas6, Axl receptor and hypoxia inducible factor -1 alpha are expressed together, and hypoxia strengthens the signal transduction of Gas6-Axl receptor. Thus, the Gas6-TAM system plays a regulatory role in erythropoiesis, and may be affected by hypoxia. We combine the etiology of CMS and the main blood system. Pathophysiological features, a hypothesis is proposed that the expression level and activity of Gas6-TAM system components in circulating blood and / or bone marrow cells / cells in CMS patients are abnormal. Abnormal Gas6-TAM system may be related to the increase of red blood cells, especially in the paracrine / autocrine mechanism of bone marrow, which promotes erythrocyte proliferation and causes the increase of red blood cells. Determination of HB, HCT and other parameters, ELISA method was used to determine the level of Gas6 protein in bone marrow and blood; RT-PCR method was used to detect Gas6, TAM receptor (Tyro3, Axl and Mer) m RNA level. The possible role of bone marrow, peripheral blood cell Gas6 and its TAM receptor on the increase of erythrocyte. Methods 20 cases of CMS patients were used as the research object (Study Group), 20 healthy people who lived at the same altitude for more than 3 years were used as the control group. The parameters of HB, HCT, Sa O2 were measured, and ELISA method was used to determine the level of Gas6 protein in the bone marrow and blood; RT-PCR method was used. Detect the expression level of Gas6, TAM receptor (Tyro3, Axl and Mer) m RNA in bone marrow mononuclear cells. Calculate the bone marrow blood gradient of Gas6 (bone marrow concentration minus blood concentration) when necessary. The expression level of CMS bone marrow Mer m RNA[0.39 (0.31)%] was lower than that of the control group [0.97 (0.92)%], the difference was statistically significant (P0.05) in the.CMS group, the bone marrow Axl m RNA[(0.39 + 0.45)%, Gas6 m (0.44 + 0.36)%] and the control group [(0.64 + 0.55)%], [(0.58 + 0.34)%], and the difference was not statistically significant (35.64 + 9.12) Group bone marrow Gas6 protein [(38.94 + 5.99) pg/m L], the difference was not statistically significant (P0.05).CMS blood Gas6 protein [(35.27 + 7.43) pg/m L] and the control group blood Gas6 protein [(34.21 + 9.56) pg/m L], the difference was not statistically significant (35.64 + 9.12) The difference was not statistically significant (P0.05). There was no statistical difference between the Gas6 protein (35.64 + 9.12) pg/m L] of the control group and the Gas6 protein (34.21 + 9.56) pg/m L] in the control group (P0.05). (89.42 + 4.25)% of CMS patients, (224.75 + 16.15), (69.04 + 6.70)%, (69.04 + 6.70)%, 96.86 + 0.78) and (138 + 17.21). 0 + 2.24%), the difference was statistically significant (P0.05).CMS patients age [(47.83 + 8.11) years] compared with the control group [(47.33 + 14.21) years old], the difference was not statistically significant (P0.05). (3) the correlation analysis of each index: Gas6 m RNA, Axl m RNA in CMS patients and the control group, and the expression level of Mer m and the expression level of bone marrow and blood protein There was no correlation between the levels of HB and the levels of Gas6 m RNA, Axl m RNA, Axl m RNA, Mer m, and the expression level of bone marrow and blood protein in the bone marrow of CMS patients and the control group. The bone marrow and blood of CMS group and control group were Gas6, and there was no difference in the expression of Gas6 protein between the two groups, and there was no paracrine secretion / autocrine mechanism in the local Gas6 of the bone marrow. (3) the Gas6 m RNA in the bone marrow MNC of the CMS patients and the control group was Gas6 m RNA, Axl m RNA, and there was no correlation between the expression level of bone marrow and blood protein and the level of the marrow. There is no correlation between Gas6 and its receptors.
【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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