文献类型：期刊文献

中文题名：基于lncRNA H19/miR-19b3p/FTH1轴探讨归芪益元膏联合顺铂对Lewis肺癌小鼠的干预效应及机制

英文题名：Exploration on the Intervention Effect and Mechanism of Guiqi Yiyuan Ointment Combined with Cisplatin on Lewis Lung Cancer Mice Based on lncRNA H19/miR-19b3p/FTH1 Axis

作者：薛春霞[1];梁建庆[1,2];张媛媛[1];靳银霞[1];李尚[1];章溥[1];杨楠[1];李金田[3];李娟[1]

第一作者：薛春霞

机构：[1]甘肃中医药大学基础医学院,甘肃兰州730000;[2]敦煌医学与转化教育部重点实验室,甘肃兰州730000;[3]甘肃中医药大学中医临床学院,甘肃兰州730000

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2024

卷号：31

期号：8

起止页码：90

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

收录：CSTPCD;;CSCD:【CSCD_E2023_2024】；

基金：国家自然科学基金(82160929);甘肃中医药大学中医学一级学科“岐黄英才”导师专项基金硕导项目(ZYXKSD-202211);甘肃省研究生“创新之星”项目(2023CXZX-749)。

语种：中文

中文关键词：肺癌;归芪益元膏;顺铂;小鼠;lncRNAH19/miR-19b3p/FTH1轴

外文关键词：lung cancer;Guiqi Yiyuan Ointment;cisplatin;mice;lncRNA H19/miR-19b3p/FTH1 axis

摘要：目的基于lncRNAH19/miR-19b3p/FTH1轴探讨归芪益元膏联合顺铂对Lewis肺癌小鼠的抑瘤作用及机制。方法60只SPF级雄性C57BL/6小鼠随机取10只作为空白组,其余50只皮下接种Lewis肺癌细胞复制肺癌小鼠模型。将成模小鼠随机分为模型组、顺铂组和中药低、中、高剂量联合顺铂组,每组10只,顺铂组予顺铂5 mg/kg腹腔注射,中药低、中、高剂量联合顺铂组予归芪益元膏1.75、3.5、7.0 g/kg灌胃联合顺铂5mg/kg腹腔注射,空白组和模型组予等体积生理盐水灌胃,连续14d。观察小鼠一般状况,测量小鼠瘤质量并计算抑瘤率、脾脏指数和胸腺指数,HE染色观察肿瘤组织病理形态,检测肿瘤组织丙二醛(MDA)、还原型谷胱甘肽(GSH)、过氧化氢(H2O_(2))、亚铁离子(Fe^(2+))含量,免疫组化和Western blot检测肿瘤组织核因子E2相关因子2(Nrf2)、谷胱甘肽过氧化物酶4(GPX4)、铁蛋白重链1(FTH1)、溶质载体家族7成员11(SLC7A11)蛋白表达,实时荧光定量PCR检测肿瘤组织lncRNAH19、miR-19b3p mRNA表达。结果与空白组比较,模型组小鼠体质量、脾脏指数和胸腺指数均降低(P<0.05)。与模型组比较,各给药组小鼠一般状况不同程度改善,瘤质量减少(P<0.05),脾脏指数及胸腺指数升高(P<0.05),肿瘤细胞溶解、破裂、数量减少,肿瘤组织MDA、H2O_(2)、Fe^(2+)含量升高(P<0.05),GSH含量降低(P<0.05),Nrf2、GPX4、FTH1、SLC7A11蛋白表达降低(P<0.05),lncRNAH19mRNA表达降低(P<0.05),miR-19b3pmRNA表达升高(P<0.05);与顺铂组比较,中药高剂量联合顺铂组小鼠瘤质量减少(P<0.05),体质量、脾脏指数和胸腺指数升高(P<0.05),肿瘤组织MDA、H2O_(2)、Fe^(2+)含量升高(P<0.05),GSH含量降低(P<0.05),Nrf2、FTH1、SLC7A11、GPX4蛋白表达降低(P<0.05),lncRNAH19 mRNA表达降低(P<0.05),miR-19b3p mRNA表达升高(P<0.05)。结论归芪益元膏联合顺铂对Lewis肺癌小鼠具有明显抑瘤作用,其作用机制可能与调节lncRNAH19/miR-19b3p/FTH1轴相关铁死亡分子表达有关。
Objective To explore the inhibitory effect of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung cancer mice and its mechanism based on the lncRNA H19/miR-19b3p/FTH1 axis.Methods Totally 60 SPF grade male C57BL/6 mice were randomly selected as blank group,and Lewis lung cancer mouse model was replicated in the remaining 50 mice.The modeled mice were randomly divided into model group,cisplatin group,and TCM low-,medium-and high-dosage combined with cisplatin group,with 10 mice in each group.The cisplatin group was given intraperitoneal injection of cisplatin 5 mg/kg,while the TCM low-,medium-and high-dosage combined with cisplatin group were given Guiqi Yiyuan Ointment 1.75,3.5,7.0 g/kg by gavage combined with intraperitoneal injection of cisplatin 5 mg/kg,the blank group and model group were given equal volume of normal saline by gavage for 14 consecutive days.The general condition of mice was observed,the tumor mass of mice was measured,and the tumor inhibition rate,spleen index,and thymus index were calculated,HE staining was used to observe the pathological changes of tumor tissue,and the contents of malondialdehyde(MDA),reduced glutathione(GSH),hydrogen peroxide(H2O_(2)),and ferrous ions(Fe^(2+))were detected in the tumor tissue,immunohistochemistry and Western blot were used to detect the expression of nuclear factor E2 related factor 2(Nrf2),glutathione peroxidase 4(GPX4),ferritin heavy chain 1(FTH1)and solute carrier family 7 member 11(SLC7A11)protein in tumor tissue,real time fluorescence quantitative PCR was used to detect the expression of lncRNA H19 and miR-19b3p mRNA in tumor tissue.Results Compared with the blank group,the body mass,spleen index and thymus index of mice in the model group were decreased(P<0.05).Compared with the model group,the mental state and tumor histopathological morphology of mice in each administration group were improved to different degrees,the tumor mass of mice was reduced(P<0.05),the spleen index and the thymus index of mice increased(P<0.05),tumor cell lysis,rupture,and decrease in quantity,the contents of MDA,H2O_(2),Fe^(2+)in tumor tissue increased(P<0.05),while GSH content decreased(P<0.05),the expression of Nrf2,GPX4,FTH1,SLC7A11 protein in tumor tissue decreased(P<0.05),the lncRNA H19 mRNA expression decreased(P<0.05),miR-19b3p mRNA expression increased(P<0.05).Compared with the cisplatin group,the tumor mass of mice in TCM high-dosage combined with cisplatin group reduced(P<0.05),the body mass,spleen index and thymus index increased(P<0.05),the contents of MDA,H2O_(2),Fe^(2+)in tumor tissue of mice increased(P<0.05),the content of GSH decreased(P<0.05),the expression of Nrf2,FTH1,SLC7A11,GPX4 protein expression decreased(P<0.05),lncRNA H19 mRNA expression decreased(P<0.05),miR-19b3p mRNA expression increased(P<0.05).Conclusion Guiqi Yiyuan Ointment combined with cisplatin can significantly inhibit the tumor of Lewis lung cancer mice,and its mechanism may be related to regulating the expression of ferroptosis molecules related to the lncRNA H19/miR-19b3p/FTH1 axis.