滨州医学院学报2025,Vol.48Issue(2):119-124,129,7.DOI:10.19739/j.cnki.issn1001-9510.2025.02.002
高血糖合并原位结直肠癌小鼠模型的建立及蛋白质组学研究
Establishment and proteomic analysis of hyperglycemia combined with in-situ colorectal cancer mouse model
摘要
Abstract
Objective To establish a mouse model of hyperglycemia complicated with in-situ colorectal cancer(CRC),and compare the differentially expressed proteins in the CRC mucosa between hyperglycemic mice and normal blood glucose mice through proteomic analysis.Methods C57BL/6 mice were randomly divided into the control group(group N),the normal blood glucose experimental group(AD)and the hyperglycemic experimental group(AD+STZ).The control group received a conven-tional feeding regimen,while the experimental group received intraperitoneal injection of azomethane oxide(AOM)and drinking dextran sodium sulfate(DSS)solution to construct an inflammation related CRC mouse model.The hyperglycemic experimental group received intraperitoneal injection of streptozotocin(STZ)at the 4th week.At the 10th week of modeling,colonic samples were taken from mice and colonic morphological changes were observed by macroscopic observation and microscopic examination with H&E staining to detect histopathological changes.The colonic mucosa and tumor tissues were selected for differential pro-teomic analysis by high resolution mass spectrometry,and KEGG signal pathway enrichment analysis and STRING database pro-tein interaction network analysis were performed.Results Compared with the N and AD groups,the weight of mice in AD+STZ group decreased significantly(P<0.05),the length of colon shortened(P<0.01)and the weight increased(P<0.05),and the number of tumor formation increased significantly.Proteomic results showed that compared with group N,there were 540 dif-ferentially expressed proteins in AD group and 793 differentially expressed proteins in AD+STZ group,among which 73 proteins were only differentially expressed in AD+STZ group.The differences between AD group and AD+STZ group were mainly con-centrated in protein export,ribosomes,protein processing in the endoplasmic reticulum and other metabolically related pathways.Pdia6,Rpn1,Sec63 and other proteins with strong correlation with these differentially expressed proteins were found in the inter-action network of protein processing pathways in the endoplasmic reticulum.Conclusion A mouse model of hyperglycemia com-bined with in-situ CRC was successfully established,and the characteristic differentially expressed proteins were found through proteomic analysis.These differentially expressed proteins may be potential targets for diagnosis,prognosis monitoring and pre-vention of hyperglycemia combined with CRC.关键词
结直肠癌/糖尿病/小鼠模型/蛋白质组学分析Key words
colorectal cancer/diabetes mellitus/mouse model/proteomic analysis分类
基础医学引用本文复制引用
冯可树,李泽,姜昊哲,林露,姜文国..高血糖合并原位结直肠癌小鼠模型的建立及蛋白质组学研究[J].滨州医学院学报,2025,48(2):119-124,129,7.基金项目
山东省自然科学基金面上项目(ZR2023MH218) (ZR2023MH218)