摘要
目的 从外周血中寻找吸烟成瘾的潜在标志物.方法 通过转录组测序分析仅在吸烟未成瘾和吸烟成瘾人群淋巴细胞和中性粒细胞中有显著差异表达的基因.通过构建大鼠烟碱条件性位置偏爱模型,获取其腹侧被盖区和伏隔核区及其外周血淋巴细胞,采用蛋白免疫印迹对差异基因蛋白的表达进行检测.结果 吸烟未成瘾和吸烟成瘾人群外周血淋巴细胞和中性粒细胞中均有114种差异表达基因;其中CBSL、CPXM1、DEFA4、DTL和TRPV4基因差异表达更为显著.与对照组相比,烟碱条件性位置偏爱组大鼠腹侧被盖区的6种蛋白表达量均无显著差异(P＞0.05,F(5,30)=0.99),伏隔核区的△FosB 和 CREB 蛋白表达水平显著上调(P＜0.05,F(5,36)=5.195).结论 CBSL、CPXM1、DEFA4、DTL、TRPV4、MAOB、ICAM1、CREB5和FOS这几种基因以及外周血CREB蛋白均可能是烟碱成瘾的潜在标志物.
Abstract
Objective The aim is to search for potential markers of tobacco addiction in peripheral blood.Methods Transcriptome sequencing analysis was conducted to identify genes with significantly differential expression specifically in lymphocytes and neutrophils between smoking non-addicted and addicted individuals.By establishing a nicotine-induced conditioned place preference(CPP)model in rats,their ventral tegmental area(VTA),nucleus accumbens(NAc),and peripheral blood lymphocytes were obtained.Western blotting was then employed to detect the expression of proteins corresponding to the differentially expressed genes.Results A total of 114 genes showed differential expression in peripheral blood lymphocytes and neutrophils between non-addicted smokers.Among them,the differential expression of CBSL,CPXM1,DEFA4,DTL,and TRPV4 genes was more significant.Compared with the control group,there was no significant difference in the expression of the six proteins in the ventral tegmental region of rats in the nicotine-conditioned place preference group(P＞0.05,F(5,30)=0.99).Still,the protein expression of ΔFosB and CREB in the nucleus accumbens was significantly up-regulated(P＜0.05,F(5,36)=5.195).Conclusion BSL,CPXM1,DEFA4,DTL,TRPV4,MAOB,ICAM1,CREB5 and FOS,and CREB protein in peripheral blood may be potential markers of nicotine addiction.
基金项目
中国烟草总公司科技重大专项项目(110202001031JY-14)
NETL
NSTL
万方数据