首页|基于STAT3信号通路探讨花椒精油吸嗅改善CAC小鼠免疫微环境的机制

基于STAT3信号通路探讨花椒精油吸嗅改善CAC小鼠免疫微环境的机制

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目的:探讨花椒精油吸嗅对结肠炎相关性结直肠癌(CAC)小鼠免疫微环境的影响及作用机制.方法:将70只小鼠随机分为空白组(10只)、模型组(20只)、溶媒组(20只)、花椒精油组(20只).除空白组,其余组采用氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)造模,第7天开始给药,溶媒组给予2％Tween-80雾化,花椒精油组给予5％花椒精油雾化.隔日1次,15 min/次,直至14周.监测体质量变化,计算结肠指数、脾脏指数、肿瘤负荷,HE染色检测结肠与脾脏组织病理,Ki67免疫组化与TUNEL免疫荧光染色检测结肠组织细胞增殖与凋亡水平,免疫组化检测中性粒细胞和巨噬细胞浸润程度以及信号转导及转录激活因子3(STAT3)、p-STAT3表达水平.结果:与模型组比较,花椒精油组小鼠体质量下降情况改善,脾脏指数显著降低(P＜0.05),结肠肿瘤负荷显著减少(P＜0.05),结肠黏膜炎症浸润与肿瘤增生程度减轻,脾脏髓外造血减少,结肠肿瘤细胞增殖率显著降低(P＜0.05),凋亡率显著增加(P＜0.01),中性粒细胞与巨噬细胞密度显著降低(P＜0.05)、p-STAT3组织化学评分显著降低(P＜0.05).结论:雾化吸入花椒精油能够减少结肠肿瘤形成与免疫炎症细胞浸润,延缓CAC进程,其作用机制可能与调控STAT3信号通路、重塑积极的免疫微环境有关.
Discussion on the mechanism of improving the immune microenvironment of CAC mice by inhaling the essential oil of Zanthoxyli Pericarpium based on STAT3 signaling pathway
Objective:To explore the effect and mechanism of inhaling the essential oil of Zanthoxyli Pericarpium(ZPEO)on the immune microenvironment of colitis-associated colorectal cancer(CAC)mice.Methods:A total of 70 mice were randomly divided into blank group(n=10),model group(n=20),solvent group(n=20),and ZPEO group(n=20).Except for blank group,the CAC model was induced with azoxymethane(AOM)/dextran sodium sulphate(DSS)in all groups.Administration was started on day 7 with 2％Tween-80 nebulized in the solvent group and 5％ZPEO nebulized in the ZPEO group.It was given once every other day for 15 min/time until 14 weeks.Changes in body mass were monitored;colonic index,splenic index and tumor load were calculated;histopathology of colon and spleen was detected using HE staining;cell proliferation and apoptosis in colon tissue were measured by Ki67 immunohistochemistry and TUNEL immunofluorescence staining;the infiltration of neutrophils and macrophages and the expression of STAT3 and p-STAT3 were determined by immunohistochemistry.Results:Compared with the model group,decreased body mass and spleen index of mice in ZPEO group improved(P＜0.05),colon tumor load decreased(P＜0.05);inflammatory infiltration and tumor hyperplasia in the colonic mucosa alleviated,extramedullary haemopoiesis in the spleen reduced;proliferation rate of colonic tumor decreased(P＜0.05),apoptosis rate increased(P＜0.01),the density of neutrophils and macrophages reduced(P＜0.05),and histochemical score of p-STAT3 decreased(P＜0.05).Conclusion:Atomized inhalation of the essential oil of Zanthoxyli Pericarpium can reduce the formation of colon tumors and the infiltration of immune inflammatory cells to delay the progression of CAC,and its mechanism might be related to its regulation of STAT3 signaling pathway and the remodeling of a positive immune microenvironment.

Colitis-associated colorectal cancerEssential oil of Zanthoxyli PericarpiumAtomized inhalationImmune microenvironmentSTAT3 signaling pathway

刘宏、陈芜、林俊芝、祝捷、由凤鸣、郑川

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成都中医药大学附属医院,代谢性疾病中医药调控四川省重点实验室,成都 610075

成都中医药大学肿瘤研究所,成都 610075

结肠炎相关性结直肠癌 花椒精油 雾化吸入 免疫微环境 STAT3信号通路

四川省国际科技创新合作项目中国博士后科学基金第71批面上资助地区专项

2019YFH01522022MD713683

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子：1.135
ISSN：1673-1727
年,卷(期)：2024.39(1)
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