本文選題：年齡效應 + 淋巴細胞　； 參考：《中國科學技術大學》2009年碩士論文

【摘要】： 衰老是一種遺傳因素和外界環(huán)境共同影響的,由在細胞水平上發(fā)生的變化逐步積累并最終表現在組織器官水平上的現象。在衰老的過程中,有許多因素會誘發(fā)細胞內遺傳物質的損傷(基因突變、端粒縮短、細胞內調控機制失調等)。在這些與衰老有關的遺傳物質的損傷中,最為明顯的表現就是在細胞分裂過程中染色體分離異常的年齡效應以及非整倍體細胞的年齡效應。 在本次研究中,我們采用cytokinesis-block method分別從染色體分離異常的角度以及非整倍體細胞命運的角度探討在中國男性外周血淋巴細胞中的年齡效應: 1.運用cytokinesis-block method,我們首次研究并報道了在中國男性的外周血淋巴細胞中染色體分離異常的年齡效應。本文收集了14名老年(60-70歲之間)和10名青年(22-26歲之間)中國男性的外周血,從中分離得到淋巴細胞并進行培養(yǎng),以松胞素B阻滯細胞質分裂而獲得雙核細胞,用人X、Y和2號染色體特異的著絲粒探針進行熒光原位雜交,以檢測X和Y染色體的分離異常。發(fā)現:老年人淋巴細胞中,X染色體(老年組9.2±3.2‰,青年組1.1±0.9‰, P0.001)和Y染色體丟失的頻率(老年組2.5±1.9%,年輕組0.2±0.3‰,P0.001)較青年人顯著升高; X染色體(老年組16.5±3.4‰,年輕組3.5±1.1‰,P0.001)和Y染色體不分離的頻率(老年組7.2±2.6‰,年輕組2.4±1.3‰,P0.001)也隨著年齡增加而顯著升高;在老年人和青年人的淋巴細胞中,無論X染色體還是Y染色體,其染色體不分離的頻率均顯著高于丟失的頻率;觀察到的多種染色體分離異常同時發(fā)生的頻率也顯著高于相應的預期頻率。這些結果表明,年齡顯著影響中國男性淋巴細胞中X和Y染色體的正常分離;與染色體丟失相比,染色體不分離是中國男性性染色體分離異常的是主要類型;細胞內負責染色體精確分離的機制出現異�？赡軙瑫r引起X和Y染色體的丟失及不分離。 2.我們分析發(fā)生了染色體分離異常的有絲分裂理論上應產生的子細胞,在理論上應產生的子細的群體中Chr X-細胞在淋巴細所占比例值為25.7‰,而我們在體內的外周血淋巴細胞群體中實際并未觀察到Chr X-細胞,從這一結果中,我們發(fā)現X染色體的缺失對男性淋巴細胞的存活有極大的影響。此外,通過比較進入分裂形成雙核的非整倍體淋巴細胞以及未進入分裂的單核非整倍體淋巴細胞,我們探討了不同染色體的缺失或者獲得對淋巴細胞分裂能力的影響。結果表明,在老年人的幾種非整倍體外周血淋巴細胞中,Y染色體缺失的淋巴細胞(Chr Y-)的分裂能力最強(P0.001,χ2-test),與之不同的是,在年輕人的非整倍體外周血淋巴細胞中,Y染色體缺失的淋巴細胞(Chr Y-)的分裂能力與X染色體獲得的淋巴細胞(Chr X+)相似(P=0.46,χ~2-test),而Y染色體獲得的淋巴細胞(Chr Y+)的分裂能力最弱(P0.001,χ~2-test)。這一結果說明了在老年人和青年人中Y染色體對細胞分裂能力的不同影響,證實了Y染色體隨年齡增長對細胞的功能和重要性的變化。綜上所述,不同染色體的缺失或者獲得對細胞命運的影響是不同的,并且這些染色體在年輕人和老年人細胞中的作用和影響也不同。
[Abstract]:Aging is a combination of genetic factors and external environment, which gradually accumulates at the level of cell and eventually appears at the level of tissue and organ. In the process of aging, there are many factors that induce the damage of genetic material in cells (gene mutation, telomere shortening, and dysregulation of intracellular regulation mechanism, etc.). The most obvious manifestation of the damage to genetic material related to aging is the age effect of abnormal chromosomal separation during cell division and the age effect of aneuploidy.
In this study, we used cytokinesis-block method to investigate the age effect in Chinese male peripheral blood lymphocytes from the angle of chromosomal segregation and the fate of aneuploidy, respectively.
1. using cytokinesis-block method, we first studied and reported the age effect of abnormal chromosomal segregation in the peripheral blood lymphocytes of Chinese men. This article collected the peripheral blood of 14 elderly (60-70 years old) and 10 young Chinese men (22-26 years old). X, Y, and chromosome 2 specific centromere probes were used for fluorescence in situ hybridization to detect the abnormal separation of X and Y chromosomes by blocking the cytoplasmic division. The frequencies of X chromosomes (aged 9.2 + 3.2%, 1.1 + 0.9 per thousand, P0.001) and Y loss were found in the lymphocytes of the elderly (2.5 + 1.9% in the elderly group). The young group was 0.2 + 0.3 per thousand, P0.001) was significantly higher than that of young people, and the frequency of X chromosome (aged 16.5 + 3.4%, 3.5 + 1.1 per 1000, P0.001) and Y chromosome non separation (aged 7.2 + 2.6 per 1000, young group 2.4 + 1.3 per thousand, P0.001) also increased with age; in the lymphocytes of the elderly and young people, no matter X chromosome or Y The frequencies of chromosomes were significantly higher than those of the lost frequency; the frequencies of abnormal chromosomal abnormalities observed at the same time were also significantly higher than the corresponding expected frequencies. These results suggest that age significantly affects the normal separation of X and Y chromosomes in Chinese male lymphocytes; chromosomes are not compared with chromosome loss. Separation is the main type of male sex chromosome segregation in China, and the abnormal mechanism of chromosomal separation in cells may cause the loss and separation of X and Y chromosomes at the same time.
2. we analyzed the subcells in the theory of mitosis that had occurred in chromosomal separation. In theory, the proportion of Chr X- cells in the subfine group was 25.7 per 1000, and we did not observe Chr X- cells in the peripheral blood lymphocyte population in the body. In this result, we found X The loss of chromosomes has a great effect on the survival of male lymphocytes. In addition, we have explored the loss of chromosomes or the effect on the mitosis of the cells by comparing into the division of the diploid aneuploidy lymphocytes and the mononuclear cells that have not entered the division. The Y chromosome missing lymphocyte (Chr Y-) has the strongest splitting capacity in several aneuploidy peripheral blood lymphocytes (P0.001, X 2-test) in several aneuploidy peripheral blood lymphocytes of the year, which is different from that of the Y chromosome missing lymphocyte (Chr Y-) and the X chromosome obtained lymphocyte (Chr X+) in the young's aneuploidy peripheral blood lymphocytes. Similar (P=0.46, X ~2-test), and the Y chromosome acquired lymphocyte (Chr Y+) is the weakest (P0.001, Chi ~2-test). This result illustrates the different effects of Y chromosome on cell division in the elderly and young people, and confirms the changes in the function and importance of the Y chromosome with age increasing. The effects of chromophore deletion or acquisition on cell fate are different, and these chromosomes play different roles in young and elderly cells.
【學位授予單位】：中國科學技術大學
【學位級別】：碩士
【學位授予年份】：2009
【分類號】：R392.12

【共引文獻】

相關期刊論文 前5條

1 余從年,方思鳴,周光云,A.Wojcik,C．Streffer;應用原位雜交技術檢測X射線誘發(fā)的特定染色體的微核率[J];中國組織化學與細胞化學雜志;1998年02期

2 王崢;江小華;張歡;史慶華;;紡錘體組裝檢驗點[J];細胞生物學雜志;2009年02期

3 ;Effects of age on segregation of the X and Y chromosomes in cultured lymphocytes from Chinese men[J];遺傳學報;2009年08期

4 王亞紅;孫興華;朱志圖;哈敏文;;BUB1與APC蛋白在不同乳腺組織中的表達及臨床意義[J];中國癌癥雜志;2008年12期

5 別黎;張博;趙剛;;有絲分裂紡錘體檢驗點基因在腫瘤中的作用研究進展[J];中華臨床醫(yī)師雜志(電子版);2012年02期

相關博士學位論文 前3條

1 高華;BACP在細胞基因組穩(wěn)定性中的作用研究[D];中國協和醫(yī)科大學;2006年

2 汪旭;葉酸及其部分代謝因素對人類基因組穩(wěn)定性的作用機制研究[D];復旦大學;2005年

3 別黎;跨平臺整合微陣列數據篩選與膠質瘤級別相關基因的實驗研究[D];吉林大學;2011年

相關碩士學位論文 前1條

1 徐遠久;自然流產胚胎絨毛組織紡錘體檢查點基因表達研究[D];重慶醫(yī)科大學;2007年

，

本文編號：2012402