[1]袁芸菲,刘清娥,李 森,等.桔梗多糖经血小板衍生生长因子受体/血管内皮生长因子受体途径调控巨噬细胞对溃疡性结肠炎模型小鼠黏膜损伤的改善作用及机制研究[J].陕西医学杂志,2025,54(3):301-306.[doi:DOI:10.3969/j.issn.1000-7377.2025.03.003]
　YUAN Yunfei,LIU Qing'e,LI Sen,et al.Effect and mechanism of platycodon grandiflorum polysaccharides regulating macrophages through PDGF/VEGF receptor pathway in improving mucosal damage in ulcerative colitis model mice[J].,2025,54(3):301-306.[doi:DOI:10.3969/j.issn.1000-7377.2025.03.003]
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桔梗多糖经血小板衍生生长因子受体/血管内皮生长因子受体途径调控巨噬细胞对溃疡性结肠炎模型小鼠黏膜损伤的改善作用及机制研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年3期
页码:
301-306
栏目:
基础研究
出版日期:
2025-03-05

文章信息/Info

Title:
Effect and mechanism of platycodon grandiflorum polysaccharides regulating macrophages through PDGF/VEGF receptor pathway in improving mucosal damage in ulcerative colitis model mice
作者:
袁芸菲; 刘清娥; 李 森; 常 健; 田利英; 张夏霞
(邯郸市中心医院消化内二科,河北 邯郸 056004)
Author(s):
YUAN Yunfei; LIU Qing'e; LI Sen; CHANG Jian; TIAN Liying; ZHANG Xiaxia
(The Second Department of Gastroenterology,Handan Central Hospital,Handan 056004,China)
关键词:
溃疡性结肠炎;  桔梗多糖;  巨噬细胞;  血小板衍生生长因子受体-α;  血管内皮生长因子受体-3;  小鼠
Keywords:
Ulcerative colitis;  Platycodon grandiflorum polysaccharide;  Macrophage;  Platelet-derived growth factor receptor-α;  Vascular endothelial growth factor receptor-3;  Mouse
分类号:
R 285.5
DOI:
DOI:10.3969/j.issn.1000-7377.2025.03.003
文献标志码:
A
摘要:
目的:观察桔梗多糖对溃疡性结肠炎(UC)模型小鼠黏膜损伤的改善作用,并探究其机制。方法:将32只小鼠随机分为对照组(非UC)、模型组、桔梗多糖低剂量组和高剂量组,每组8只。1周适应性饲养后,除对照组外,其余三组小鼠通过葡聚糖硫酸钠(DSS)灌胃建立UC模型。桔梗多糖低、高剂量组每日分别灌胃100、200 mg/kg桔梗多糖,其余组灌胃等量蒸馏水,每日1次,持续1周。自建模日起,监测小鼠疾病活动指数(DAI)评分。末次给药后禁食12 h,处死小鼠并取材,测量结肠长度; HE染色分析结肠黏膜病理; F4/80、诱导型一氧化氮合酶(iNOS)免疫组化染色识别M1型巨噬细胞; 酶联免疫吸附试验(ELISA)检测小鼠结肠组织巨噬细胞M2型极化标志白细胞介素-4(IL-4)、IL-10水平; Western blot检测小鼠结肠组织转化生长因子-β(TGF-β)、血小板衍生生长因子受体-α(PDGFR-α)和血管内皮生长因子受体-3(VEGFR-3)蛋白表达情况。结果:与对照组比较,模型组小鼠DAI评分增高(P<0.01); 与模型组比较,桔梗多糖低剂量组给药第6天起、高剂量组给药第4天起DAI评分明显降低(均P<0.05)。与模型组相比,桔梗多糖低、高剂量组结肠长度更长(均P<0.05); 结肠组织黏膜病理形态均不同程度改善; F4/80、iNOS免疫组化染色的细胞阳性率更低(均P<0.01); 结肠组织IL-4、IL-10表达水平升高,且TGF-β、PDGFR-α、VEGFR-3蛋白表达也升高(均P<0.05)。结论:桔梗多糖通过调控巨噬细胞向抗炎M2型极化改善UC模型小鼠黏膜损伤,其作用机制可能与上调PDGFR/VEGFR信号有关。
Abstract:
Objective:To observe the effect of platycodon grandiflorum polysaccharides in improving mucosal injury in ulcerative colitis(UC)model mice and explore its mechanism.Methods:A total of 32 mice were randomly divided into control group(non-UC),model group,platycodon grandiflorum polysaccharides low-dose group and high-dose group,with 8 mice in each group.After 1 week of adaptive feeding,except the control group,the other three groups were administrated with DSS to establish UC model.The low- and high- dose groups were given 100,200 mg/kg of platycodon grandiflorum polysaccharides per day,respectively,and the other groups were given the same amount of distilled water once a day for 1 week.The DAI score was monitored from the modeling date.After the last administration,the mice were fasted for 12 hours,and the colonic length was measured; colon mucosal pathology was analyzed by HE staining; M1 macrophages were identified by F4/80 and iNOS immunohistochemical staining; ELISA was used to detect the levels of polarization markers IL-4 and IL-10; the expression of TGF-β,PDGFR-α and VEGFR-3 proteins in colon tissue was detected by Western blot.Results:Compared with control group,DAI score of model group was increased(P<0.01).Compared with model group,DAI scores in low-dose group from day 6 and high-dose group from day 4 were significantly decreased(all P<0.05).Compared with model group,the colon length was longer in low- and high-dose groups(all P<0.05); the pathological morphology of colonic mucosa was improved in different degree; the positive rate of F4/80 and iNOS immunohistochemical staining was lower(all P<0.01); the expression levels of IL-4 and IL-10 in colon tissues were increased,and the protein expressions of TGF-β,PDGFR-α and VEGFR-3 were also increased(all P<0.05).Conclusion:Platycodon grandiflorum polysaccharides can improve the mucosal damage of UC model mice by regulating macrophage polarization towards anti-inflammatory M2 type,and its mechanism may be related to up-regulation of PDGFR/VEGFR signaling.

参考文献/References:

[1] FEUERSTEIN J D,MOSS A C,FARRAYE F A.Ulcerative colitis[J].Mayo Clin Proc,2019,94(7):1357-1373.
[2] KINUGASA T,AKAGI Y.Status of colitis-associated cancer in ulcerative colitis[J].World J Gastrointest Oncol,2016,8(4):351-357.
[3] YAMAZAKI M,CHUNG H,XU Y,et al.Trends in the prevalence and incidence of ulcerative colitis in Japan and the US[J].Int J Colorectal Dis,2023,38(1):135.
[4] SLEIMAN J,BASSI M,TSIPOTIS E,et al.Medical treatment options for ulcerative colitis[J].Clin Colon Rectal Surg,2022,35(6):428-436.
[5] 孙萍,徐慧,黄艳红,等.桔梗化学成分的提取方法和药理作用概述[J].中国酿造,2022,41(9):18-23.
[6] LIU Y,DONG Y,SHEN W,et al.Platycodon grandiflorus polysaccharide regulates colonic immunity through mesenteric lymphatic circulation to attenuate ulcerative colitis[J].Chin J Nat Med,2023,21(4):263-278.
[7] ZOU X,TANG X Y,QU Z Y,et al.Targeting the PDGF/PDGFR signaling pathway for cancer therapy:A review[J].Int J Biol Macromol,2022,202(4):539-557.
[8] LAI W,XIAN C,CHEN M,et al.Single-cell and bulk transcriptomics reveals M2d macrophages as a potential therapeutic strategy for mucosal healing in ulcerative colitis[J].Int Immunopharmacol,2023,121(4):110509.
[9] 张罡,叶桐,窦丹波.基于NF-κB相关信号通路探讨常用中药治疗溃疡性结肠炎研究进展[J].陕西中医,2023,44(6):818-821.
[10] 高三明.臭氧联合培菲康治疗溃疡性结肠炎临床疗效及对细胞因子IL-6、TGF-1水平的影响[J].陕西医学杂志,2013,42(7):895-897.
[11] 高亚,曹晖,宾东华,等.芍药汤治疗湿热内蕴型溃疡性结肠炎疗效及对患者炎症因子和T淋巴细胞亚群的影响[J].陕西中医,2024,45(10):1336-1339,1344.
[12] 赵苗,刘莉莎,何德才.从中医圆运动理论论治溃疡性结肠炎[J].中医学报,2024,39(8):1657-1662.
[13] NEURATH M F,CHIRIAC M T.Targeting immune cell wiring in ulcerative colitis[J].Immunity,2019,51(5):791-793.
[14] DELFINI M,STAKENBORG N,VIOLA M F,et al.Macrophages in the gut:Masters in multitasking[J].Immunity,2022,55(9):1530-1548.
[15] MURRAY P J.Macrophage polarization[J].Annu Rev Physiol,2017,79(4):541-566.
[16] LONG J,LIU X K,KANG Z P,et al.Ginsenoside Rg1 ameliorated experimental colitis by regulating the balance of M1/M2 macrophage polarization and the homeostasis of intestinal flora[J].Eur J Pharmacol,2022,917(4):174742.
[17] FU Y,LI J,LI M,et al.Umbilical cord mesenchymal stem cells ameliorate inflammation-related tumorigenesis via modulating macrophages[J].Stem Cells Int,2022,22(4):1617229.
[18] LARSON C,ORONSKY B,CARTER C A,et al.TGF-beta:A master immune regulator[J].Expert Opin Ther Targets,2020,24(5):427-438.
[19] FUNA K,SASAHARA M.The roles of PDGF in development and during neurogenesis in the normal and diseased nervous system[J].J Neuroimmune Pharmacol,2014,9(2):168-181.
[20] ZHENG H,AN M,LUO Y,et al.PDGFRα+ITGA11+fibroblasts foster early-stage cancer lymphovascular invasion and lymphatic metastasis via ITGA11-SELE interplay[J].Cancer Cell,2024,42(4):682-700.
[21] APTE R S,CHEN D S,FERRARA N.VEGF in signaling and disease:Beyond discovery and development[J].Cell,2019,176(6):1248-1264.
[22] XIN H,ZHONG C,NUDLEMAN E,et al.Evidence for pro-angiogenic functions of VEGF-Ax[J].Cell,2016,167(1):275-284.
[23] KUONQUI K,CAMPBELL A C,SARKER A,et al.Dysregulation of lymphatic endothelial VEGFR3 signaling in disease[J].Cells,2023,13(1):68.
[24] KIM H,KIM C Y,KIM D,et al.Protective effects of imatinib on a DSS-induced colitis model through regulation of apoptosis and inflammation[J].In Vivo,2024,38(5):2310-2317.
[25] HUANG C,TAN H,WANG J,et al.β-hydroxybutyrate restrains colitis-associated tumorigenesis by inhibiting HIF-1α-mediated angiogenesis[J].Cancer Lett,2024,59(3):216940.

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备注/Memo

备注/Memo:
[基金项目]河北省医学科学研究课题(20241263)
更新日期/Last Update: 2025-03-05