石见穿诱导铁死亡抑制小鼠食管癌发生发展的研究  

Study on the Inhibition of Esophageal Carcinoma Development in Mice by Salvia Chinensia Benth Induced Ferroptosis

作　　者：林鑫荣 贾蕾 李丽峰 黄鸣 吴忠冰 李晶 LIN Xinrong;JIA Lei;LI Lifeng;HUANG Ming;WU Zhongbing;LI Jing(College of Integrated Chinese and Western Medicine,Hebei Medical University,Shijiazhuang 050011,China;Department of Traditional Chinese Medicine,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,China)

机构地区：[1]河北医科大学中西医结合学院,河北省石家庄市050011 [2]河北医科大学第四医院中医科,河北省石家庄市050011

出　　处：《中国全科医学》2024年第30期3784-3789,共6页Chinese General Practice

基　　金：国家自然科学基金资助项目(81973761)。

摘　　要：背景食管癌是一种在中国乃至全球范围内常见的消化道恶性肿瘤,具有很高的发病率和致死率。石见穿(SJC)作为传统中药,其清热解毒、活血镇痛之功常用于食管癌的治疗中。药理实验研究证明,SJC具有抗癌性,可有效治疗多种恶性肿瘤。目的基于铁死亡探讨SJC抑制C57小鼠食管原位癌发生发展的作用和机制。方法2022年2月—2023年2月选取SPF级C57BL/6雌鼠90只,随机分为对照组(Control组,n=15)、单纯4NQO诱癌组(4NQO组,n=25)、4-硝基喹啉N-氧化物(4NQO)+SJC低剂量组[4NQO/SJC(91 mg)组,n=25]和4NQO+SJC高剂量组[4NQO/SJC(182 mg)组,n=25]。采用4NQO诱导的方式进行C57小鼠食管癌原位模型的制备。观察小鼠活动情况,记录其精神状况和进食饮水情况,每隔8周分组测量小鼠体质量并进行记录。32周后进行食管组织苏木素-伊红(HE)染色和病理学分析。测定食管组织Fe^(2+)、谷胱甘肽(GSH)和丙二醛(MDA)含量,采用蛋白质印迹法检测小鼠食管组织中核受体共激活因子4(NCOA4),谷胱甘肽过氧化物酶4(GPX4)蛋白质的表达水平。采用Kaplan-Meier法绘制小鼠的生存曲线,生存曲线的比较采用Breslow检验。结果造模8、16、24、32周4NQO组、4NQO/SJC(91 mg)组、4NQO/SJC(182 mg)组小鼠体质量低于Control组,32周4NQO/SJC(91 mg)组、4NQO/SJC(182 mg)组小鼠体质量高于4NQO组(P<0.05)。Breslow检验结果显示,4组小鼠生存曲线比较,差异有统计学意义(χ^(2)=9.907,P=0.019)。HE染色结果可见,4NQO组小鼠食管上皮组织呈现异常增生,细胞排列紊乱,出现角化珠等异常病理改变;与4NQO组比较,4NQO/SJC(91 mg)组和4NQO/SJC(182 mg)组食管上皮组织病理学改变明显改善。4NQO组、4NQO/SJC(91 mg)组、4NQO/SJC(182 mg)组Fe^(2+)、MDA均低于Control组,GSH均高于Control组(P<0.05);4NQO/SJC(91 mg)组、4NQO/SJC(182 mg)组Fe^(2+)、MDA均高于4NQO组,GSH均低于4NQO组(P<0.05);4NQO/SJC(182 mg)组Fe^(2+)、MDA均高于4NQO/SJC(91 mg)组,GSH均Background Esophageal carcinoma is a common malignant tumor of the gastrointestinal tract in China and even globally,with a high incidence and mortality rate.As a traditional Chinese medicine,Salvia chinensia Benth(SJC)has the effects of clearing heat and detoxifying,promoting blood circulation and easing pain in the treatment of esophageal cancer.Pharmacological experimental studies have proved that SJC has anticancer properties and can effectively treat a variety of malignant tumors.Objective To explore the effect and mechanism of SJC in the inhibition of carcinoma in situ esophageal cancer development of C57 mice based on ferroptosis.Methods Ninety SPF grade C57BL/6 female mice were selected from February 2022 to February 2023 and randomly divided into Control group(n=15),simple 4-Nitroquinoline N-oxide(4NQO)-induced cancer group(4NQO group,n=25),4NQO+low-dose SJC group[4NQO/SJC(91 mg)group,n=25]and 4NQO+high dose SJC group[4NQO/SJC(182 mg)group,n=25].The preparation of in situ model of esophageal cancer in C57 mice was carried out using 4NQO induction.The activities of the mice were observed,their mental state,food and water intake were recorded,and the body mass of the mice was measured and recorded at 8-week intervals.Hematoxylin-eosin(HE)staining and pathological analysis of esophageal tissue were performed after 32 weeks.The contents of Fe^(2+),glutathione(GSH)and malondialdehyde(MDA)in esophageal tissues were determined,and the expression levels of nuclear receptor coactivator 4(NCOA4)and glutathione peroxidase 4(GPX4)in esophageal tissues of mice were detected by western blot.Kaplan-Meier method was used to plot the survival curves of mice,and Breslow test was used to compare the survival curves.Results The body mass of mice in 4NQO group,4NQO/SJC(91 mg)group and 4NQO/SJC(182 mg)group at 8,16,24 and 32 weeks of modeling was lower than that in Control group.The body mass of 4NQO/SJC(91 mg)group and 4NQO/SJC(182 mg)group at 32 weeks was higher than that of 4NQO group(P<0.05).The results of Breslow test sh

关 键 词：食管癌 铁死亡 石见穿 原位癌诱导模型 谷胱甘肽过氧化物酶4 核受体共激活因子4 

分 类 号：R735.1[医药卫生—肿瘤]