基于NF-κB/NLRP3炎症小体信号通路探讨胃癌前病变的发病机制及胃复春胶囊的作用机制  

Pathogenesis of precancerous lesions of gastric cancer and treatment mechanism of Weifuchun Capsules via NF-κB/NLRP3 inflammasome signaling pathway

作　　者：杜羽佳 任娅迪 庄严 李恩泽 苗俊豪 于春月 DU Yu-jia;REN Ya-di;ZHUANG Yan;LI En-ze;MIAO Jun-hao;YU Chun-yue(College of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;School of Acupuncture-Moxibustion and Tuina,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin Key Laboratory of Modern Chinese Medicine Theory of Innovation and Application,Tianjin 301617,China)

机构地区：[1]天津中医药大学中医学院,天津301617 [2]天津中医药大学针灸推拿学院,天津301617 [3]天津市现代中医理论创新转化重点实验室,天津301617

出　　处：《中国中药杂志》2025年第5期1236-1246,共11页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金青年科学基金项目(82104819)。

摘　　要：探讨核因子-κB(NF-κB)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体信号通路在胃癌前病变中的发病机制,并进一步探讨胃复春胶囊治疗胃癌前病变的潜在分子机制。将90只SPF级Wistar雄性大鼠随机分为正常饲养组和造模组,正常饲养组常规饮食;造模组采用N-甲基-N′-硝基-N-亚硝基胍(MNNG)综合造模法建立胃癌前病变病证结合动物模型:120μg·mL-1MNNG自由饮用、0.05%雷尼替丁饲料联合饥饱失常。15周后,正常饲养组随机分为空白组、空白-NF-κB激活剂组(C-BA组)和空白-NF-κB抑制剂组(C-PDTC组);造模组继续造模并随机分为模型组、胃复春胶囊组(WFC组)、模型-NF-κB激活剂组(M-BA组)和模型-NF-κB抑制剂组(M-PDTC组)。空白组和模型组予无菌水灌胃,每日1次;WFC组按照成人等效剂量(体质量60 kg)的6倍(432 mg·kg^(-1))给药,每日1次;C-BA组和M-BA组予NF-κB激活剂桦木酸(BA)腹腔注射,10 mg·kg^(-1),每周2次;C-PDTC组和M-PDTC组予NF-κB抑制剂吡咯烷二硫代甲酸铵(PDTC)腹腔注射,50 mg·kg^(-1),每周2次;干预4周后取材。苏木素-伊红(HE)和过碘酸雪夫(AB-PAS)染色法观察胃黏膜病理组织学变化并评分,酶联免疫吸附法(ELISA)测定胃组织中炎性细胞因子白细胞介素(IL)-1β、IL-6、IL-18、肿瘤坏死因子-α(TNF-α)、IL-10的水平,蛋白免疫印迹法检测胃黏膜中NF-κB/NLRP3炎症小体相关蛋白的表达水平,免疫组化法检测胃黏膜中NF-κB/NLRP3炎症小体相关蛋白的阳性表达面积。结果显示,与空白组相比,模型组、C-BA组和M-BA组黏膜炎症、炎症活动程度、腺体萎缩及肠上皮化生评分显著升高,模型组和M-BA组异型增生评分显著升高。与模型组相比,WFC组黏膜炎症、炎症活动程度及腺体萎缩评分显著降低,肠上皮化生及异型增生评分降低。与空白组相比,模型组和C-BA组胃组织中IL-1β、IL-6、IL-18、TNF-α水平显著升高;模型组IL-10水平显著升高;�This study aims to investigate the pathogenesis of precancerous lesions of gastric cancer(PLGC)and explore the potential molecular mechanism of Weifuchun Capsules(WFC)in treating PLGC via the nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3)inflammasome signaling pathway.Ninety male SPF-grade Wistar rats were randomized into a normal feeding group and a modeling group.The normal feeding group received a regular diet,while the modeling group was subjected to the disease-syndrome combined modeling of PLGC.Specifically,the rats had free access to the water containing 120μg·mL-1 N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)and received a diet containing 0.05% ranitidine in an irregular feeding pattern(alternations between fasting and overfeeding).After 15 weeks,the rats in the normal feeding group were randomized into control,control-NF-κB activator betulinic acid(C-BA),and control-NF-κB inhibitor pyrrolidine dithiocarbamaten(C-PDTC)groups.Meanwhile,the rats in the modeling group continuously underwent the modeling procedure and were randomized into model,WFC,model-NF-κB activator(M-BA),and model-NF-κB inhibitor(M-PDTC)groups.The model group and control group were given aseptic water by intragastric administration,once a day.WFC was given at a dose(432 mg·kg^(-1))6 times the equivalent dose for adults(body weight:60 kg)by gavage,once a day.The rats in the C-BA and M-BA groups were administrated with BA by intraperitoneal injection at a dose of 10 mg·kg^(-1),twice a week.The rats in the C-PDTC and M-PDTC groups were administrated with PDTC by intraperitoneal injection at a dose of 50 mg·kg^(-1),twice a week.The interventions were carried out for 4 weeks.Histopathological changes of the gastric mucosa were observed and scored by hematoxylin-eosin(HE)and alcian blue-periodic acid Sthiff(AB-PAS)staining.The levels of inflammatory cytokines including interleukin(IL)-1β,IL-6,IL-18,tumor necrosis factor-alpha(TNF-α),and IL-10 in the gastric tissue were determined by enzyme-linked immunosorbent assay(ELIS

关 键 词：胃癌前病变 NF-ΚB NLRP3炎症小体 胃复春胶囊 炎-癌转化 

分 类 号：R285.5[医药卫生—中药学]