半夏泻心汤对胃癌大鼠铁死亡相关分子的影响

Effects of Banxia Xiexin Decoction on Ferroptosis-Related Molecules in Gastric Cancer Rats

目的:探讨半夏泻心汤对N-甲基-N′-硝基-N-亚硝基胍(MNNG)诱导的胃癌大鼠铁死亡相关分子的影响。方法:将50只SD大鼠随机分为空白组、模型组、半夏泻心汤组。空白组大鼠正常饲养,其他两组使用“MNNG灌胃+自由饮用法”造模40周,诱导胃癌模型。观察各组胃组织形态,苏木素-伊红(HE)染色观察胃病理组织学情况,免疫组化检测核因子E2相关因子2(NRF2)、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(FTH1)表达水平。结果:第52周末,空白组大鼠无胃部肿物,模型组4只大鼠出现前胃肿物;半夏泻心汤组2只大鼠出现前胃肿物;病理组织学观察发现,模型组4只大鼠出现鳞状细胞癌,2只大鼠出现前胃鳞状上皮乳头状瘤,半夏泻心汤组1只出现鳞状细胞癌,1只出现前胃鳞状上皮乳头状瘤;免疫组化结果发现,模型组Nrf2、SLC7A11、GPX4、FTH1平均光密度较空白组显著升高(P<0.01),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<0.01)。结论:半夏泻心汤可调节胃癌大鼠Nrf2、SLC7A11、GPX4、FTH1表达水平,诱导胃癌铁死亡。

Objective:To investigate the effects of Banxia Xiexin Decoction on ferroptosis-related molecules in gastric cancer rats induced by N-methyl-N′-nitro-N-nitrosoguanidine(MNNG).Methods:Fifty SD rats were randomly divided into a blank group,a model group,and a Banxia Xiexin Decoction group.Rats in the blank group were fed normally,while the rats in other two groups were modeled for 40 weeks using the“MNNG gavage+free drinking method”to induce gastric cancer.Gastric tissue morphology was observed,and hematoxylin-eosin(HE)staining was used to examine gastric pathological histology.Immunohistochemistry was employed to detect the expression levels of nuclear factor erythroid 2-related factor 2(NRF2),solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),and ferritin heavy chain 1(FTH1).Results:At the end of week 52,no gastric tumors were observed in the blank group,while four rats in the model group developed foregut tumors,and two rats in the Banxia Xiexin Decoction group developed foregut tumors.Pathological histological examination revealed that four rats in the model group had squamous cell carcinoma,and two rats had foregut squamous epithelial papilloma,while one rat in the Banxia Xiexin Decoction group had squamous cell carcinoma and one had foregut squamous epithelial papilloma.Immunohistochemistry results showed that the average optical density of NRF2,SLC7A11,GPX4,and FTH1 in the model group was significantly higher than in the blank group(P<0.05),while the average optical density of these markers was significantly lower in the Banxia Xiexin Decoction group compared to the model group(P<0.05).Conclusion:Banxia Xiexin Decoction can regulate the expression levels of NRF2,SLC7A11,GPX4,and FTH1 in gastric cancer rats,inducing ferroptosis in gastric cancer.