参白颗粒介导细胞焦亡通路阻断胃癌前病变炎癌转化作用机制的研究  

Research on the mechanism of ginseng white granules through the cell pyroptosis pathway in blocking the transformation of precancerous lesions of gastric cancer from inflammation to cancer

作　　者：张希颜 曹峻文 张忠绵 陶婧娜 张丽菊 陈嘉钦 王岚 林子力 张晶潾 贺柏翔 李志红[1] Zhang Xiyan;Cao Junwen;Zhang Zhongmian;Tao Jingna;Zhang Liju;Chen Jiaqin;Wang Lan;Lin Zili;Zhang Jinglin;He Baixiang;Li Zhihong(Digestive Department,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院消化科,北京100700

出　　处：《消化肿瘤杂志（电子版）》2024年第4期448-456,共9页Journal of Digestive Oncology(Electronic Version)

基　　金：国家自然科学基金(82074187);北京自然科学基金(7232290);北京中医药大学东直门医院临床研究和成果转化能力提升试点项目(DZMG-MLZY-23009)。

摘　　要：目的探讨参白颗粒阻断胃癌前病变(precancerous lesions of gastric cancer,PLGC)炎癌转化的作用机制。方法运用N-甲基-N'-硝基-N-亚硝基胍(N-methyl-N'-nitro-N-nitrosoguanidine,MNNG)复合造模法构建PLGC大鼠模型,分别给予参白颗粒等效剂量(参白颗粒等效剂量组,n=10)、参白颗粒低剂量(参白颗粒低剂量组,n=10)、中成药对照药摩罗丹(摩罗丹药组,n=10)、西药对照药替普瑞酮(替普瑞酮对照药组,n=10)进行为期12周的药物干预,模型组(n=10)不进行给药干预。病理检测观察大鼠胃黏膜改善情况。通过免疫组织化学、蛋白质印迹法、酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测各组NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)、消皮素D(gasdermin D,GSDMD)、半胱氨酸天冬氨酸水解酶(cysteinyl aspartate specific proteinase,Caspase)-1及白介素-1β(interleukin-1β,IL-1β)的表达情况。结果病理观察发现参白颗粒等效剂量组大鼠的胃黏膜改善较其他各组明显。免疫组织化学结果提示参白颗粒等效剂量组的NLRP3、Caspase-1、IL-1β蛋白表达量较模型组降低(P<0.05);蛋白质印迹法检测发现参白颗粒等效剂量组的NLRP3、Caspase-1、GSDMD蛋白表达水平较模型组低(P<0.05);ELISA结果显示参白颗粒等效剂量组的IL-1β浓度较模型组低(P<0.05)。结论参白颗粒可以介导NLRP3炎症小体,抑制细胞焦亡,调控下游蛋白Caspase-1及GSDMD表达水平,阻碍炎症因子释放,减轻组织炎症,达到干预PLGC进展的目的。Objective To explore the mechanism of ginseng white granules blocking the process of precancerous lesions of gastric cancer(PLGC)inflammation-cancer transformation.Method The PLGC rat model was constructed by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG),with ginseng white granules equivalent dose(ginseng white granules equivalent dose group,n=10),ginseng white granules low dose(ginseng white granules low dose group,n=10),Chinese patent medicine control drug Morodan(Morodan control group,n=10)and western medicine control drug Teprenone(Teprenone control group,n=10)given for a period of 12 weeks.The model group(n=10)was without drug intervention.The improvement of gastric mucosa in each group was observed by pathological detection.The expression of NOD-like receptor thermal protein domain associated protein 3(NLRP3),gasdermin D(GSDMD),cysteinyl aspartate specific proteinase-1(Caspase-1)and interleukin-1β(IL-1β)in each group were detected by immunohistochemical,western blot and enzyme linked immunosorbent assay(ELISA).Result Pathological detection revealed that the improvement of gastric mucosa in the ginseng white granules equivalent dose group was more obvious than other groups.Immunohistochemical result demonstrated that the expression of NLRP3,Caspase-1 and IL-1βwere decreased in the ginseng white granules equivalent dose group,compared to the model group(P<0.05).Western blot showed that the expression of NLRP3,Caspase-1 and GSDMD were decreased in the ginseng white granules equivalent dose group,compared to the model group(P<0.05).The level of IL-1βdetected by ELISA in the ginseng white granules equivalent dose group was lower than that in the model group(P<0.05).Conclusion Ginseng white granules can mediated NLRP3 inflammasome to inhibit pyroptosis,regulate the expression level of downstream protein Caspase-1 and GSDMD,hinder the release of inflammatory factors,reduce tissue inflammation,and achieve the purpose of intervening in the progression of PLGC.

关 键 词：癌前病变 炎癌转化 NOD样受体热蛋白结构域相关蛋白3 参白颗粒 细胞焦亡 

分 类 号：R285.5[医药卫生—中药学]