首页|健脾化瘀解毒方抑制巨噬细胞焦亡治疗胃癌前病变的机制

健脾化瘀解毒方抑制巨噬细胞焦亡治疗胃癌前病变的机制

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目的:探讨健脾化瘀解毒方通过抑制巨噬细胞焦亡治疗胃癌前病变(GPL)的机制.方法:空白组小鼠常规饲养,造模组予以N-甲基-N-亚硝基脲(MNU)自由饮用隔日禁食法构建GPL模型,随机分为模型组,健脾化瘀解毒方高、低剂量组和维酶素组,每组12只,分别进行干预后,HE染色、AB-PAS染色观察小鼠胃黏膜组织病理学变化,Western Blot、RT-qPCR检测细胞焦亡相关指标、免疫荧光染色观察CDX2、Ki67、F4/80表达情况及F4/80与NLRP3共定位情况.体外构建J774A.1焦亡模型,予健脾化瘀解毒方含药血清干预,观察细胞焦亡相关分子表达情况.结果:与空白组比较,GPL小鼠胃黏膜NLRP3、Caspase-1、GSDMD-N、CDX2、Ki67、F4/80表达显著升高(P＜0.01),NLRP3与F4/80存在共定位现象,集中分布于黏膜层.经健脾化瘀解毒方干预后,上述分子表达下降(P＜0.01,P＜0.05),且NLRP3与F4/80共定位现象散在分布.体外实验中,与空白组比较,模型组NLRP3、GSDMD-N、IL-1 β、IL-18表达升高(P＜0.01),PI染色阳性细胞比例增加(P＜0.01),健脾化瘀解毒方可减少上述分子表达(P＜0.01,P＜0.05),减少PI染色阳性细胞比例(P＜0.01,P＜0.05).结论:健脾化瘀解毒方可通过抑制巨噬细胞焦亡治疗GPL.
Mechanism of Jianpi Huayu Jiedu Formula ameliorating gastric precancerous lesions through inhibiting macrophage pyroptosis
Objective:To explore the mechanism of Jianpi Huayu Jiedu Formula(JPHYJD)ameliorating gastric precancerous lesions(GPL)through inhibiting macrophage pyroptosis.Methods:Mice in control group were fed regularly and others were exposed to MNU and were fed every other day to construct GPL models and were divided into model group,JPHYJD high-dose group,JPHYJD low-dose group and Vitacoenzyme(VIT)group randomly,with 10 in each group.HE staining and AB-PAS staining were used to evaluate the effect of JPHYJD.The expression of pyroptosis-related molecules were observed through Western Blot and RT-qPCR.CDX2,Ki67,F4/80 and the colocalization of F4/80 and NLRP3 were checked through immunofluorescent staining.J774A.1 cells were exposed to LPS and ATP to construct pyroptosis models and then JPHYJD-contained serum.Results:Compared with the control group,the expression of NLRP3,Caspase-1,GSDMD-N,CDX2,Ki67 and F4/80 in model group increased(P＜0.01).The colocalization of F4/80 and NLRP3 were observed and concentrated in the mucosal layer.After treated by JPHYJD,molecules above decreased(P＜0.01,P＜0.05)and the colocalization only scattered.In vitro,compared with the control group,there showed a higher level of NLRP3,GSDMD-N,IL-1 β and IL-18(P＜0.01),and more PI-positive cells in model group(P＜0.01),which were decreased by JPHYJD(P＜0.01,P＜0.05).Conclusion:JPHYJD could ameliorate GPL through inhibiting macrophage pyroptosis.

Gastric precancerous lesions(GPL)Jianpi Huayu Jiedu FormulaMacrophagePyroptosisInflammation-carcinoma transition

张丹、张喜、倪家慧、杨良俊、刘伟、潘华峰

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广州中医药大学,广州 510006

浙江省立同德医院,杭州 310012

广州中医药大学第一附属医院,岭南医学研究中心,广州 510006

胃癌前病变 健脾化瘀解毒方 巨噬细胞 细胞焦亡 炎-癌转化

国家自然科学基金面上项目国家自然科学基金青年科学基金项目广东省重点领域研发计划项目广东省基础与应用基础研究基金项目广州市科学技术局基础研究计划省部共建中医湿证国家重点实验室开放课题面上项目国家中医药管理局中医药创新团队及人才支持计划项目

81973816820043002020B11111000112023A15150111072023A04J1169SZ2022KF17ZYYCXTD-C-202208

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(8)