本文選題：慢性高原病 + 紅細(xì)胞增多��； 參考：《青海大學(xué)》2015年碩士論文

【摘要】：背景慢性高原病(chronic mountain sickness,CMS)是長期生活在海拔高度2500米以上地區(qū)的移居者或世居者,對高原低氧環(huán)境逐漸失去習(xí)服而發(fā)生的臨床綜合征,又稱Monge病,曾稱高原紅細(xì)胞增多癥(high altitude polycythemia,HAPC),以紅細(xì)胞過度增生、低氧血癥為特征,常伴有肺動脈高壓。CMS紅細(xì)胞過度積累的機制尚未闡明,研究提示存在非紅細(xì)胞生成素(erythropoietin,EPO)依賴性調(diào)控機制。近年研究顯示,造血組織、造血細(xì)胞和骨髓基質(zhì)細(xì)胞表達(dá)Gas6蛋白和TAM受體的全部成員,提示Gas6-TAM受體參與造血調(diào)控。有資料證明,在前列腺癌組織中,Gas6、Axl受體與低氧誘導(dǎo)因子-1α共同表達(dá),低氧強化Gas6-Axl受體的信號轉(zhuǎn)導(dǎo)。由此可見,Gas6-TAM系統(tǒng)在紅系造血中發(fā)揮調(diào)控作用,且可能受低氧的影響。我們結(jié)合CMS的病因和血液系統(tǒng)主要的病理生理特點,提出一個假設(shè),CMS患者循環(huán)血液和/或骨髓組織/細(xì)胞中Gas6-TAM系統(tǒng)成分的表達(dá)水平和活性異常,異常的Gas6-TAM系統(tǒng)可能與紅細(xì)胞增多有關(guān),尤其骨髓局部Gas6以旁分泌/自分泌機制促進(jìn)紅細(xì)胞增生,導(dǎo)致紅細(xì)胞增多。目的 測定HB、HCT等參數(shù),采用ELISA法測定骨髓液和血液Gas6蛋白質(zhì)水平;RT-PCR法檢測骨髓單個核細(xì)胞Gas6、TAM受體(Tyro3,Axl和Mer)m RNA水平。必要時計算Gas6濃度的骨髓-血液梯度(骨髓液濃度減去血液濃度),并進(jìn)行對比分析和相關(guān)性分析,分析CMS患者骨髓、外周血細(xì)胞Gas6及其TAM受體對紅細(xì)胞增多的可能作用。方法 以CMS患者為20例為研究對象(研究組),以居住同一海拔高度地區(qū)3年以上的健康人20名為對照組。測定HB、HCT、Sa O2等參數(shù),采用ELISA法測定骨髓液和血液Gas6蛋白質(zhì)水平;RT-PCR法檢測骨髓單個核細(xì)胞Gas6、TAM受體(Tyro3,Axl和Mer)m RNA表達(dá)水平。必要時計算Gas6的骨髓-血液梯度(骨髓液濃度減去血液濃度)。進(jìn)行比較分析和相關(guān)指標(biāo)之間的相關(guān)性分析。結(jié)果 ①骨髓Mer m RNA、Axl m RNA、Gas6 m RNA、骨髓及外周血Gas6蛋白表達(dá)水平:CMS骨髓Mer m RNA[0.39(0.31)%]表達(dá)水平低于對照組[0.97(0.92)%],差異有統(tǒng)計學(xué)意義(P0.05)。CMS組骨髓Axl m RNA[(0.39±0.45)%]、Gas6 m RNA[(0.44±0.36)%]與對照組[(0.64±0.55)%]、[(0.58±0.34)%]比較,差異無統(tǒng)計學(xué)意義(P0.05)。CMS骨髓Gas6蛋白[(35.64±9.12)pg/m L]與對照組骨髓Gas6蛋白[(38.94±5.99)pg/m L]比較,差異無統(tǒng)計學(xué)意義(P0.05)。CMS血液Gas6蛋白[(35.27±7.43)pg/m L]與對照組血液Gas6蛋白[(34.21±9.56)pg/m L]比較,差異無統(tǒng)計學(xué)意義(P0.05)。CMS骨髓Gas6蛋白[(35.64±9.12)pg/m L]與CMS血液Gas6蛋白[(35.27±7.43)pg/m L]比較,差異無統(tǒng)計學(xué)意義(P0.05)。對照組骨髓Gas6蛋白[(35.64±9.12)pg/m L]與對照組血液Gas6蛋白[(34.21±9.56)pg/m L]比較,差異無統(tǒng)計學(xué)意義(P0.05)。②CMS患者Sa O2、HB、HCT分別為(89.42±4.25)%、(224.75±16.15)g/L、(69.04±6.70)%,與對照組(96.86±0.78)%、(138.00±17.21)g/L、(39.90±2.24)%比較,差異有統(tǒng)計學(xué)意義(P0.05)。CMS患者年齡[(47.83±8.11)歲]與對照組[(47.33±14.21)歲]比較,差異無統(tǒng)計學(xué)意義(P0.05)。③各指標(biāo)間相關(guān)性分析:CMS患者及對照組骨髓MNC中Gas6 m RNA、Axl m RNA、Mer m RNA表達(dá)水平及骨髓及血液Gas6蛋白表達(dá)水平與HB水平間均無相關(guān)性(均P0.05),且CMS患者及對照組骨髓MNC中Gas6 m RNA、Axl m RNA、Mer m RNA表達(dá)水平及骨髓及血液Gas6蛋白表達(dá)水平相互間亦無相關(guān)性(均P0.05)。結(jié)論 ①CMS組及健康對照組骨髓均表達(dá)Gas6及其受體Axl、Mer,但CMS組Mer m RNA表達(dá)水平較對照組降低。②CMS組及對照組骨髓及血液均表達(dá)Gas6,兩組間Gas6蛋白表達(dá)水平無差異,且未發(fā)現(xiàn)骨髓局部Gas6存在旁分泌/自分泌機制。③CMS患者及對照組骨髓MNC中Gas6 m RNA、Axl m RNA、Mer m RNA、骨髓及血液Gas6蛋白表達(dá)水平與HB水平間均無相關(guān)性,且Gas6及其受體相互間亦無相關(guān)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.
【學(xué)位授予單位】：青海大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R594.3

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