基于转录组测序探讨湿热蕴结证结直肠腺瘤癌变的生物学基础及参白解毒方作用机制  

Biological Foundation of Colorectal Adenoma Carcinogenesis in Damp-heat Accumulation Syndrome Based on Transcriptome Sequencing and Mechanism of Shenbai Jiedu Prescription

作　　者：陶玉泉 程海波[1,2] 范旻旻 余成涛 李柳 张烨[1,2] 倪明欣 沈梦 TAO Yuquan;CHENG Haibo;FAN Minmin;YU Chengtao;LI Liu;ZHANG Ye;NI Mingxin;SHEN Meng(Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor,The First Clinical College of Nanjing University of Chinese Medicine,Nanjing 210023,China;Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]南京中医药大学第一临床医学院,江苏省中医药防治肿瘤协同创新中心,南京210023 [2]南京中医药大学附属医院,南京210029

出　　处：《中国实验方剂学杂志》2024年第19期48-54,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点研发计划项目(2017YFC1700602);国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202208);国家中医药管理局高水平中医药重点学科建设项目(国中医药人教函[2023]85号);江苏高校优势学科建设工程项目(PAPD);江苏高校“青蓝工程”项目(苏教师函[2023]27号);江苏省高等学校基础学科(自然科学)研究面上项目(22KJB310003);江苏省中医药科技发展计划项目(MS2022001)。

摘　　要：目的:探讨结直肠腺瘤湿热蕴结证的生物学基础及临床有效方药参白解毒方可能的抗肿瘤作用机制。方法:临床获取2019年2月至2020年12月江苏省中医院招募的符合纳入标准的结直肠腺瘤湿热蕴结证患者8例、非湿热蕴结证者11例和结直肠癌患者10例,对3组患者组织进行转录组测序,筛选证候间及疾病间差异表达基因,并对证候和疾病间差异基因取交集,进一步筛选在非湿热蕴结证、湿热蕴结证和结直肠癌患者中依次递增或依次递减的差异基因,进行功能富集分析和信号通路富集分析。采用实时荧光定量聚合酶链式反应(Real-time PCR)检测参白解毒方对上述关键差异基因表达的影响。结果:湿热蕴结证和非湿热蕴结证对比,筛选出差异表达基因共384个,其中表达上调基因203个,表达下调基因181个;结直肠癌与湿热蕴结证结直肠腺瘤比较,筛选出差异表达基因共2965个,其中表达上调基因2460个,表达下调基因505个;将2组差异基因取交集,并筛选同向变化的差异基因共58个;基因本体功能主要富集在UDP-半乳糖:β-N-乙酰葡萄糖胺β-1,3-半乳糖基转移酶活性、N-乙酰乳糖胺β-1,3-N-乙酰葡糖胺转移酶活性和聚N-乙酰乳糖胺生物合成过程;京都基因与基因组百科全书(KEGG)信号通路主要富集在鞘糖脂生物合成-珠蛋白和等珠蛋白系列、鞘糖脂生物合成-乳酸和新乳酸系列和白细胞介素(IL)-17信号通路。参白解毒方可明显抑制FOSB和B3GALT5等参与富集的关键基因的表达(P<0.05),且具有浓度依赖性。结论:糖脂代谢可能是结直肠腺瘤湿热蕴结证的生物学基础,参白解毒方可能通过下调FOSB和B3GALT5的表达抑制结直肠癌的发生。Objective:To explore the biological foundation of colorectal adenoma in damp-heat accumulation syndrome and the possible anti-tumor mechanism of Shenbai Jiedu prescription.Method:Eight patients with colorectal adenoma in damp-heat accumulation syndrome,11 patients with non-damp-heat accumulation syndrome,and 10 patients with colorectal cancer recruited by Jiangsu Provincial Hospital of Traditional Chinese Medicine from February 2019 to December 2020 meeting the inclusion criteria were clinically obtained,and the tissue of the three groups of patients was subjected to transcriptome sequencing to screen for the differentially expressed genes between the syndrome and the diseases.The intersection of the differentially expressed genes between the syndrome and the disease was taken for further screening of the differentially expressed genes sequentially increasing or sequentially decreasing in patients with non-damp-heat accumulation syndrome,damp-heat accumulation syndrome,and colorectal cancer,and functional enrichment analysis and signaling pathway enrichment analysis were carried out.Real-time polymerase chain reaction(Realtime PCR)was used to detect the effect of Shenbai Jiedu prescription on the expression of the above key differential genes.Result:By comparing the damp-heat accumulation syndrome and non-damp-heat accumulation syndrome,a total of 384 differentially expressed genes were screened,of which 203 were up-regulated genes,and 181 were down-regulated genes.By comparing the colorectal adenoma of colorectal cancer and damp-heat accumulation syndrome,a total of 2965 differentially expressed genes were screened,of which 2460 were up-regulated genes,and 505 were down-regulated genes.The intersection of differentially expressed genes of the two groups was taken,and a total of 58 differentially expressed genes with the same changes were screened.The gene ontology functions were mainly enriched in UDP-galactose:β-Nacetylglucosamine beta-1,3-galactosyltransferase activity,N-acetyllactosaminide beta-1,3-Nacetylgl

关 键 词：参白解毒方 结直肠腺瘤癌变 湿热蕴结证 转录组测序 证侯生物学基础 

分 类 号：R2-0[医药卫生—中医学] R22R242R285.5R574