细胞周期抑制剂SNS-032对小鼠造血干细胞生物活性的影响研究

发布时间：2018-05-24 09:40

本文选题：CDK + 造血干细胞　；参考：《中国实验血液学杂志》2013年03期

【摘要】：本研究旨在探讨SNS-032(C17H24N4O2S2)对小鼠骨髓造血干细胞(hematopoietic stem cells,HSC)细胞周期、凋亡、分化及自我更新的影响及其可能的相关机制。利用极限稀释实验检测SNS-032作用前后HSC自我更新的变化,用流式细胞术检测SNS-032作用前后小鼠骨髓细胞Lin-c-kit+Sca-1+及Lin-c-kit+Sca-1-表型细胞的细胞周期及凋亡的变化,用实时定量PCR检测SNS-032作用前后细胞周期相关基因、凋亡相关基因及HSC自我更新相关基因mRNA表达量的水平。结果显示,SNS-032处理后,小鼠骨髓细胞中HSC的自我更新能力没有明显变化;加SNS-032处理后,小鼠骨髓细胞Lin-c-kit+Sca-1+表型细胞的细胞周期无统计学意义的变化(P0.05),小鼠骨髓Lin-c-kit+Sca-1-表型细胞的G1期细胞增多(P0.05);小鼠骨髓细胞Lin-c-kit+Sca-1+表型细胞和Lin-c-kit+Sca-1-表型细胞的细胞凋亡增多,与对照相比均无显著性差异(P0.05)。小鼠骨髓细胞经SNS-032处理后,HSC周期相关基因CDK1、CDK2、CDK7、p27的表达量均明显降低(P0.05),而CDK4,CDK6,p21,p18,p19,p16的表达与对照组相比没有明显变化(P0.05)。凋亡相关基因Bcl-2、Bax、Puma和p53表达量与对照组相比没有明显区别(P0.05),与干细胞自我更新相关的基因中Bim,Sall4,Notch1表达量升高,但与对照组相比没有显著性差异(P0.05)。结论:SNS-032没有明显的抑制正常造血干细胞自我更新、分化作用,而且SNS-032没有明显的诱导正常造血干、祖细胞的凋亡作用。
[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.
【作者单位】：中国医学科学院、北京协和医学院血液病医院、血液学研究所、实验血液学国家重点实验室;
【基金】：科技部973项目(编号2012CB966601,2010CB945204) 自然科学基金(编号:81170465,81130074,81070390) 天津市科委自然基金重点项目(编号10JCZDJC19500,11JCZDJC27900)
【分类号】：R329.28

【相似文献】