文献类型：期刊文献

中文题名：基于转录组学-网络药理学探讨加味当归补血汤对CIPN模型小鼠神经炎症的干预机制

英文题名：Exploring the intervention mechanism of modified Danggui buxue decoction on neuroinflammation in CIPN model mice based on transcriptomics and network pharmacology

作者：张家琼[1,2,3,4];韩翼飞[1,2,3,4];宋超[1,2,3,4];陈彦文[1,4];王彦君[5];路晨霞[6];明海霞[1,2,3,4]

第一作者：张家琼

机构：[1]甘肃中医药大学基础医学院;[2]甘肃省高校重大疾病分子医学与中医药防治研究重点实验室;[3]甘肃省中药质量与标准研究重点实验室;[4]甘肃省中医药防治慢性疾病重点实验室;[5]甘肃中医药大学附属医院重症医学科;[6]甘肃百草堂医药科技有限公司,甘肃兰州730000

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2026

卷号：42

期号：3

起止页码：221

中文期刊名：细胞与分子免疫学杂志

外文期刊名：Chinese Journal of Cellular and Molecular Immunology

收录：;北大核心:【北大核心2023】；

基金：甘肃省教育厅高校产业支撑计划项目(2023CYZC-56);甘肃省科技厅自然科学基金项目(25JRRA251,25JRRA926);甘肃省中药质量与标准研究重点实验室开放基金项目(ZYZL2024-06);甘肃省“双一流”科研重点项目(GSSYLXM-05);甘肃中医药大学研究生创新创业基金项目(2026CXZX-940)。

语种：中文

中文关键词：化疗致周围神经毒性(CIPN);加味当归补血汤;背根神经节(DRG);NF-κB信号通路

外文关键词：chemotherapy-induced peripheral neurotoxicity(CIPN);modified Danggui buxue decoction;dorsal root ganglia(DRG);NF-κB signaling pathway

摘要：目的探讨加味当归补血汤干预化疗致周围神经毒性(CIPN)模型小鼠神经炎症的作用靶点。方法SPF级C57BL/6J小鼠60只,除空白组外,其余48只在腋下异位移植胃癌细胞,并随机分为4组:胃癌组、CIPN模型组、加味当归补血汤组和度洛西汀组,每组12只,除胃癌组外,其余组腹腔注射奥沙利铂构建胃癌铂类CIPN模型,药物干预组分别给予相应剂量药液灌胃,其余组灌胃等量生理盐水,每日1次,28 d后,进行行为学实验(机械痛、冷刺实验),取小鼠背根神经节(DRG)经转录组学、透射电镜(TEM)、Western blot法及实时定量PCR对相应指标进行检测。结果行为学实验结果显示:给药28 d后,与空白组相比,CIPN模型组机械痛阈值呈下降趋势,冷刺缩足次数呈上升趋势;与CIPN模型组比,胃癌组、加味当归补血汤组、度洛西汀组机械痛阈值呈上升趋势,冷刺缩足次数呈下降趋势。转录组学结果显示:加味当归补血汤可通过抑制核因子κB(NF-κB)、共济失调毛细血管扩张症突变基因(ATM)、CC趋化因子配体21(CCL21)发挥作用。网络药理学结果提示,加味当归补血汤可能通过抑制肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-6干预CIPN的发生。TEM结果显示:除空白组外,其余四组DRG内有髓神经纤维均出现异常。与空白组比,CIPN模型组有髓神经纤维出现脱髓鞘和溶解现象且髓鞘板层排列疏松,线粒体嵴断裂溶解,出现空泡化;与CIPN模型组比,加味当归补血汤组及度洛西汀组上述损伤均有所减轻。Western blot法、实时定量PCR检测结果显示:与空白组比,CIPN模型组DRG ATM、NF-κB、CCL21、TNF-α、IL-1β、IL-6蛋白和基因表达显著升高;与CIPN模型组比,胃癌组、加味当归补血汤组和度洛西汀组中ATM、NF-κB、CCL21、TNF-α、IL-1β、IL-6蛋白和基因表达显著下降。结论加味当归补血汤可改善胃癌奥沙利铂CIPN模型小鼠DRG病理损伤及疼痛症状,其机制可能与其抑制DRG NF-κB信号通路,下调ATM、NF-κB、CCL21、TNF-α、IL-1β及IL-6的表达有关。
Objective To investigate the intervention targets of modified Danggui buxue decoction on neuroinflammation in a chemotherapy-induced peripheral neuropathy(CIPN)model mice.Methods Sixty SPF-grade C57BL/6J mice were used.Except for the blank control group,the remaining 48 mice underwent ectopic transplantation of gastric cancer cells into the axilla and were randomly divided into four groups(n=12 per group):the gastric cancer group,the CIPN model group,the modified Danggui buxue decoction group,and Duloxetine group.Except for the gastric cancer group,mice in the other groups received intraperitoneal injections of oxaliplatin to establish a model of CIPN following platinum-based chemotherapy for gastric cancer.The drug intervention groups were administered their respective doses of medicinal solution by gavage,while the remaining groups received an equal volume of normal saline by gavage,once daily.After 28 days,performing behavioral experiments(mechanical pain threshold test and cold stimulation test),the dorsal root ganglia of the mice were collected for analysis of relevant indicators using transcriptomics,TEM,WB,and RT-PCR.Results Behavioral test results showed:After 28 days of administration,compared with the blank control group,the CIPN model group exhibited a downward trend in mechanical pain threshold and an upward trend in the frequency of paw withdrawal in response to cold stimulation.Compared with the CIPN model group,the gastric cancer group,modified Danggui buxue decoction group,and the Duloxetine group showed an upward trend in mechanical pain threshold and a downward trend in the frequency of paw withdrawal in response to cold stimulation.Transcriptomics results indicated that modified Danggui buxue decoctioned its effects by inhibiting NF-κB,ATM,and CCL21.Network pharmacology analysis suggested that modified Danggui buxue decoction might intervene in the occurrence of CIPN by suppressing IL-1βand IL-6 through TNF-αinhibition.TEM results revealed:Except for the blank control group,abnormal myelinated nerve fibers were observed in the dorsal root ganglia of the other four groups.Compared with the blank control group,the CIPN model group exhibited demyelination,dissolution of myelin sheaths,loosely arranged myelin lamellae,disrupted and dissolved mitochondrial cristae,and vacuolation.Compared with the CIPN model group,the modified Danggui buxue decoction group and the Duloxetine group showed alleviation of the aforementioned damage.WB and RT-PCR results showed:Compared with the blank control group,the protein and gene expression levels of ATM,NF-κB,CCL21,TNF-α,IL-1β,and IL-6 in the dorsal root ganglia of the CIPN model group were significantly increased.Compared with the CIPN model group,the protein and gene expression levels of ATM,NF-κB,CCL21,TNF-α,IL-1β,and IL-6 were significantly decreased in the gastric cancer group,modified Danggui buxue decoction group,and the Duloxetine group.Conclusion Modified Danggui buxue decoction may ameliorate pathological damage and pain symptoms in the dorsal root ganglia of a mouse model of oxaliplatin-induced peripheral neurotoxicity following gastric cancer chemotherapy.The mechanism is likely associated with the inhibition of the NF-κB signaling pathway in the dorsal root ganglia and the down regulation of ATM,NF-κB,CCL21,TNF-α,IL-1β,and IL-6 expression.