外周血中烟碱成瘾潜在生物标志物筛选研究  

Screening of potential biomarkers of nicotine addiction in peripheral blood

作　　者：程浩平 程碗燕 张森[4] 付亚宁 陈欢 侯宏卫 CHENG Hao-ping;CHENG Wan-yan;ZHANG Sen;FU Ya-ning;CHEN Huan;HOU Hong-wei(Anhui University,Hefei 230601,China;China National Tobacco Quality Supervision&Test Center,Key Laboratory of Tobacco Biological Effects,Zhengzhou 450001,China;Bejing Life Science Academy,Bejing 102200,China;Northwest University,Xi'an 710069,China)

机构地区：[1]安徽大学,合肥230601 [2]国家烟草质量监督检测中心,烟草生物学效应重点实验室,郑州450001 [3]北京生命科技研究院,北京102200 [4]西北大学,西安710069

出　　处：《中国药物依赖性杂志》2024年第5期378-386,共9页Chinese Journal of Drug Dependence

基　　金：中国烟草总公司科技重大专项项目(110202001031(JY-14))。

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。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△FosB 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.

关 键 词：烟碱成瘾 RNA测序 条件性位置偏爱模型 淋巴细胞 中性粒细胞 成瘾标志物 

分 类 号：R749[医药卫生—神经病学与精神病学]