半夏泻心汤调控铁死亡对胃癌前病变大鼠的作用机制研究  

Effect of Banxia Xiexin Decoction on Ferroptosis in Rats Models of Precancerous Lesion of Gastric Cancer

作　　者：马佳乐 梁欣奕 张馨元 冷孟桐 李慧臻[1] MA Jia-le;LIANG Xin-yi;ZHANG Xin-yuan;LENG Meng-tong;LI Hui-zhen(Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学第二附属医院,天津300250 [2]天津中医药大学,天津301617

出　　处：《时珍国医国药》2024年第7期1542-1546,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金面上项目(81573889,82274442);天津市卫生健康委员会中医药重点领域科研项目(202007);天津市卫生健康委员会中医中西医结合科研课题(2023134);天津中医药大学第二附属医院育才计划(YC-FY202301)。

摘　　要：目的探讨半夏泻心汤调节铁死亡对胃癌前病变大鼠的影响。方法将30只SD大鼠按随机分为空白组、模型组、半夏泻心汤组。空白组小鼠正常饲养,其他两组使用“MNNG多因素刺激法”造模,以构建胃癌前病变模型。采用苏木素-伊红(HE)染色光镜下观察胃黏膜病理组织学情况;qRT-PCR、Western Blot、免疫组化检测核因子E2相关因子2(N RF2)、胱氨酸/谷氨酸逆向转运蛋白溶质载体家族7成员11(SLC7A11)、谷胱甘肽过氧化物酶(GPX4)、铁蛋白重链1(F TH1)表达。结果(1)病理组织学:模型组大鼠胃黏膜可见中-重度萎缩,腺体异型增生,而半夏泻心汤组大鼠胃黏膜萎缩程度较模型组明显减轻,且无异型增生。(2)qRT-PCR:模型组大鼠NRF2、SLC7A11、GPX4、FTH1 mRNA表达较空白组显著升高(P<0.05);半夏泻心汤干预后NRF2、SLC7A11、GPX4、FTH1 mRNA表达较模型组显著降低(P<0.05)。(3)Western Blot:模型组大鼠NRF2、SLC7A11、GPX4、FTH1 mRNA蛋白较空白组显著升高(P<0.05);半夏泻心汤干预后NRF2、SLC7A11、GPX4、FTH1 mRNA蛋白较模型组显著降低(P<0.05)。(4)免疫组化:模型组胃黏膜Nrf2、SLC7A11、GPX4、FTH1平均光密度较空白组显著升高(P<0.05),半夏泻心汤干预后Nrf2、SLC7A11、GPX4、FTH1平均光密度较模型组显著降低(P<0.05)。结论胃癌前病变进展过程中存在铁死亡抑制,半夏泻心汤可通过诱导铁死亡治疗胃癌前病变,其作用机制可能与调控NRF2/GPX4信号通路有关。Objective To investigate the effect of Banxia Xiexin Decoction on ferroptosis in rats models of Precancerous lesion of gastric cancer(PLGC).Methods 30 SD rats were randomly divided into normal group,model group and Banxia Xiexin decoction group.Mice in the normal group were fed normally,and the other two groups were modeled by"MNNG multi-factor stimulation method"to construct PLCC model.HE staining was used to observe the pathological changes of gastric mucosa.The expressions of nuclear factor E2-related factor 2(NRF2),cystine/glutamate reverse transporter solute carrier family 7 member 1l(SLC7A11),glutathione peroxidase(CPX4)and ferritin heavy chain 1(FTH1)were detected by qRT-PCR,Western Blot and immunohistochemistry.Results(1)Histopathology:moderate to severe atrophy and glandular dysplasia were observed in the gastric mucosa of the model group,while the degree of gastric mucosa atrophy of the rats in Banxia Xiexin decoction group was significantly reduced compared with the model group,and no dysplasia was observed.(2)qRT-PCR:Compared with normal group,mRNA expressions of NRF2,SLC7A11,GPX4 and FTHI in model group were significantly increased(P<0.05).Compared with model group,the mRNA expressions of NRF2,SLC7A11,GPX4 and FTH1 in Banxia Xiexin Tang group were significantly decreased after intervention(P<0.05).(3)Western blot:Compared with normal group,mRNA proteins of NRF2,SLC7A11,GPX4 and FTH1 in gastric tissue of model group were significantly increased(P<0.05).Compared with model group,mRNA proteins of NRF2,SLC7A1l,GPX4 and FTHI in Banxia Xiexin Tang group were significantly decreased after intervention(P<0.05).(4)Immunohistochemistry:Compared with normal group,the average optical density of gastric mucosa Nrf2,SLC7A11,GPX4 and FTH1 in model group was significantly increased(P<0.05)Compared with model group,the average optical density of Nrf2,SLC7A11,GPX4 and FTHI of gastric mucosa in Banxia Xiexin decoction group was decreased(P<0.05).Conclusion Ferroptosis inhibition exists in the progression of PLGC.Banxia

关 键 词：半夏泻心汤 胃癌前病变 铁死亡 作用机制 

分 类 号：R285.5[医药卫生—中药学]