基于细胞因子芯片分析白蛋白结合型紫杉醇致周围神经病变的分子机制  

Mechanism of Nab-paclitaxel-induced peripheral neuropathy based on cytokine array analysis

作　　者：潘书沛 魏星 郝钰 安雷 李艳[1] 何普 赵永林 PAN Shupei;WEI Xing;HAO Yu;AN Lei;LI Yan;HE Pu;ZHAO Yonglin(Department of Radiation Oncology,Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China;Department of Obstetrics and Gynecology,Second Affiliated Hospital of Xi’an Jiaotong University;Department of Oncology,Second Affiliated Hospital of Xi’an Jiaotong University)

机构地区：[1]西安交通大学第二附属医院肿瘤放疗科,西安710004 [2]西安交通大学第二附属医院妇产科 [3]西安交通大学第二附属医院肿瘤科

出　　处：《山西医科大学学报》2023年第10期1362-1367,共6页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(82001327);陕西省自然科学基金资助项目(2023-JC-QN-0986)。

摘　　要：目的基于细胞因子芯片探究白蛋白结合型紫杉醇(nanoparticle albumin-bound paclitaxel,Nab-PTX)诱导化疗相关周围神经病变(chemotherapy-induced peripheral neuropathy,CIPN)的分子机制。方法建立CIPN大鼠模型,将8只清洁级雄性SD大鼠随机均分为实验组和对照组,实验组大鼠第1,3,5,7天腹腔注射Nab-PTX(10 mg/kg),对照组大鼠第1,3,5,7天腹腔注射同等体积生理盐水,期间观察两组大鼠状态、饮食及粪便情况,第7天分别检测实验组和对照组大鼠疼痛阈值并确定造模成功。实验第9天将两组大鼠经水合氯醛麻醉后处死,取大鼠L4-6脊髓进行细胞因子芯片检测,筛选实验组和对照组表达显著差异的蛋白;并对差异蛋白进行基因本体分析(gene ontology,GO)及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果细胞因子芯片共筛选出5个表达显著差异的蛋白:Fractalkine、Gas1、RANTES、Notch-1、Prolactin,且这5个差异蛋白在实验组表达水平均显著高于对照组(P<0.05)。GO分析显示,这5个差异蛋白主要参与调控细胞因子及其受体活性、上皮细胞增殖。KEGG通路富集结果显示,这些差异蛋白主要富集于细胞因子受体相关通路、肿瘤坏死因子(TNF)信号通路等。结论细胞因子Fractalkine、Gas1、RANTES、Notch-1、Prolactin是Nab-PTX作用的关键靶点;Nab-PTX通过调控神经上皮细胞增殖、细胞因子及其受体活性、细胞因子受体相关通路及TNF信号通路等引起CIPN。Objective To investigate the molecular mechanism of nanoparticle albumin-bound paclitaxel(Nab-PTX)inducing chemotherapy-related peripheral neuropathy(CIPN)using the cytokine array.Methods Eight male SPF SD rats were randomly divided into experimental group and control group.The rats in experimental group were intraperitoneally injected with 10 mg/kg Nab-PTX at day 1,3,5,7 to establish a CIPN model,while the rats in control group received equivalent volumes of normal saline.The status,diet and feces of rats were observed during the experiment.The pain thresholds were determined in experimental group and control group at day 7 to confirm the successful establishment of CIPN rat model.At day 9,the rats in two groups were euthanized after being anesthetized with chloral hydrate.And the L4-6 spinal cord was subjected to cytokine array to identify the differentially expressed proteins between experimental group and control group.Additionally,the proteins were analyzed by gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Results Five proteins with significantly differential expression between experimental group and control group were identified through cytokine array,which were Fractalkine,Gas1,RANTES,Notch-1,and Prolactin.The expression levels of these proteins were significantly higher in experimental group than those in control group(P<0.05).Gene ontology(GO)analysis revealed that these differential proteins mainly participated in regulating the activity of cytokines and their receptors as well as the proliferation of epithelial cells.The enrichment analysis of KEGG pathways revealed that the differentially expressed proteins were predominantly enriched in cytokine receptor-related signaling pathways and tumor necrosis factor(TNF)signaling pathway.Conclusion Fractalkine,Gas1,RANTES,Notch-1 and Prolactin may be key targets of Nab-PTX.And Nab-PTX can induce CIPN by regulating neuroepithelial cell proliferation,the activity of cytokines and their receptors,the cytokine receptor-relate

关 键 词：细胞因子芯片 化疗相关周围神经病变 白蛋白结合型紫杉醇 GO分析 KEGG通路分析 

分 类 号：R745[医药卫生—神经病学与精神病学]