本文選題：CDK + 造血干細(xì)胞　； 參考：《中國(guó)實(shí)驗(yàn)血液學(xué)雜志》2013年03期

【摘要】：本研究旨在探討SNS-032(C17H24N4O2S2)對(duì)小鼠骨髓造血干細(xì)胞(hematopoietic stem cells,HSC)細(xì)胞周期、凋亡、分化及自我更新的影響及其可能的相關(guān)機(jī)制。利用極限稀釋實(shí)驗(yàn)檢測(cè)SNS-032作用前后HSC自我更新的變化,用流式細(xì)胞術(shù)檢測(cè)SNS-032作用前后小鼠骨髓細(xì)胞Lin-c-kit+Sca-1+及Lin-c-kit+Sca-1-表型細(xì)胞的細(xì)胞周期及凋亡的變化,用實(shí)時(shí)定量PCR檢測(cè)SNS-032作用前后細(xì)胞周期相關(guān)基因、凋亡相關(guān)基因及HSC自我更新相關(guān)基因mRNA表達(dá)量的水平。結(jié)果顯示,SNS-032處理后,小鼠骨髓細(xì)胞中HSC的自我更新能力沒(méi)有明顯變化;加SNS-032處理后,小鼠骨髓細(xì)胞Lin-c-kit+Sca-1+表型細(xì)胞的細(xì)胞周期無(wú)統(tǒng)計(jì)學(xué)意義的變化(P0.05),小鼠骨髓Lin-c-kit+Sca-1-表型細(xì)胞的G1期細(xì)胞增多(P0.05);小鼠骨髓細(xì)胞Lin-c-kit+Sca-1+表型細(xì)胞和Lin-c-kit+Sca-1-表型細(xì)胞的細(xì)胞凋亡增多,與對(duì)照相比均無(wú)顯著性差異(P0.05)。小鼠骨髓細(xì)胞經(jīng)SNS-032處理后,HSC周期相關(guān)基因CDK1、CDK2、CDK7、p27的表達(dá)量均明顯降低(P0.05),而CDK4,CDK6,p21,p18,p19,p16的表達(dá)與對(duì)照組相比沒(méi)有明顯變化(P0.05)。凋亡相關(guān)基因Bcl-2、Bax、Puma和p53表達(dá)量與對(duì)照組相比沒(méi)有明顯區(qū)別(P0.05),與干細(xì)胞自我更新相關(guān)的基因中Bim,Sall4,Notch1表達(dá)量升高,但與對(duì)照組相比沒(méi)有顯著性差異(P0.05)。結(jié)論:SNS-032沒(méi)有明顯的抑制正常造血干細(xì)胞自我更新、分化作用,而且SNS-032沒(méi)有明顯的誘導(dǎo)正常造血干、祖細(xì)胞的凋亡作用。
[Abstract]:The purpose of this study was to investigate the effects of SNS-032 (C17H24N4O2S2) on the cell cycle, apoptosis, differentiation and self-renewal of hematopoietic stem cells in mice. The changes of HSC self-renewal before and after the treatment of SNS-032 and the changes of cell cycle and apoptosis of Lin-c-kit Sca-1 and Lin-c-kit Sca-1- phenotypic cells in bone marrow cells of mice before and after SNS-032 treatment were detected by limit dilution test. The expression levels of cell cycle related genes, apoptosis-related genes and HSC self-renewal related genes mRNA were detected by real-time quantitative PCR before and after SNS-032 treatment. The results showed that the self-renewal ability of HSC in bone marrow cells of mice did not change after treatment with SNS-032. There was no significant change in the cell cycle of Lin-c-kit Sca-1 phenotypic cells in mouse bone marrow cells. The number of G 1 phase cells of Lin-c-kit Sca-1- phenotypic cells in mouse bone marrow increased, while the apoptosis of Lin-c-kit Sca-1 phenotype cells and Lin-c-kit Sca-1- phenotypic cells increased in mice bone marrow cells. There was no significant difference between the two groups (P 0.05). After SNS-032 treatment, the expression of CDK1, CDK2, CDK7, p27, was significantly decreased in bone marrow cells of mice, but the expression of CDK4, CDK6, p21, p18, p19, p16 was not significantly changed compared with the control group. There was no significant difference between the apoptosis-related genes Bcl-2nBax-Puma and p53 in comparison with the control group. The expression of Bim-Sall4Ntch1 in the genes related to stem cell self-renewal was increased, but there was no significant difference compared with the control group (P 0.05). ConclusionSNS-032 did not inhibit the self-renewal and differentiation of normal hematopoietic stem cells, and SNS-032 did not induce the apoptosis of normal hematopoietic stem cells and progenitor cells.
【作者單位】： 中國(guó)醫(yī)學(xué)科學(xué)院、北京協(xié)和醫(yī)學(xué)院血液病醫(yī)院、血液學(xué)研究所、實(shí)驗(yàn)血液學(xué)國(guó)家重點(diǎn)實(shí)驗(yàn)室;
【基金】：科技部973項(xiàng)目(編號(hào)2012CB966601,2010CB945204) 自然科學(xué)基金(編號(hào):81170465,81130074,81070390) 天津市科委自然基金重點(diǎn)項(xiàng)目(編號(hào)10JCZDJC19500,11JCZDJC27900)
【分類(lèi)號(hào)】：R329.28

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