文献类型：期刊文献

中文题名：葛花解酲汤对脾虚湿热型溃疡性结肠炎“炎-癌转化”中相关原抑癌基因表达的影响

英文题名：Effect of Gehua Jiecheng Decoction on proto-tumor suppressor gene expression in the“inflammation-cancer transformation”of ulcerative colitis with spleen deficiency and damp-heat

作者：李晓玲[1];吴玉泓[2];李海龙[1];殷银霞[3];舍雅莉[1];郝民琦[4];梁永林[1]

第一作者：李晓玲

机构：[1]甘肃中医药大学基础医学院,兰州730000;[2]深圳大学附属华南医院;[3]北京中医药大学深圳医院(龙岗),深圳518111;[4]南方医科大学中西医结合医院,广州510000

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：2023

卷号：35

期号：5

起止页码：858

中文期刊名：天然产物研究与开发

外文期刊名：Natural Product Research and Development

收录：CSTPCD;;CSCD:【CSCD2023_2024】；

基金：国家自然科学基金(81860810);2021年深圳市名中医药专家学术经验传承工作室建设项目—新建项目(20111130-7);敦煌医学与转化教育部重点实验室2018年度开放基金(DHYX18-17);2022年度中医学一级学科“岐黄英才”导师专项基金博导项目(2022-5)。

语种：中文

中文关键词：葛花解酲汤;溃疡性结肠炎;炎-癌转化;脾虚湿热;原癌基因;抑癌基因

外文关键词：Gehua Jiecheng Decoction;ulcerative colitis;inflammation-cancer transformation;spleen deficiency and damp heat syndrome;proto-oncogene;tumor suppressor gene

摘要：探讨葛花解酲汤对脾虚湿热型溃疡性结肠炎(ulcerative colitis, UC)-溃疡性结肠炎相关癌变(ulcerative colitis associated carcinogenesis, UCAC)的“炎-癌转化”小鼠结肠组织中相关原抑癌基因表达的影响。80只SPF级C57BL/6雄性小鼠随机选出10只为空白组(K组),其余70只建立脾虚湿热模型。脾虚湿热模型建立后,将其随机分为模型1、2、3周期组(M1、M2、M3组)、葛花解酲汤高、中、低剂量组(G、Z、D组)和阳性对照美沙拉嗪组(Y组),10只/组,以氧化偶氮甲烷(azoxymethane, AOM)/葡聚糖硫酸钠(dextran sodium sulfate, DSS)继续建立UC-UCAC的“炎-癌转化”模型。各组给予对应药物治疗4周。观察小鼠一般状态;统计小鼠体重变化;电镜下观察小鼠结肠黏膜超微结构;WB和RT-qPCR分别检测小鼠结肠组织中c-jun、c-fos、c-myc、p53、RB1蛋白及基因的表达。与K组比,M3组小鼠一般状态差,体重增长量显著下降(P<0.01),结肠黏膜上皮细胞核染色不均匀,细胞内线粒体等见大量增生肿胀,c-jun、c-fos、c-myc蛋白及基因表达显著升高(P<0.01),p53、RB1蛋白及基因表达显著降低(P<0.01);与M3组比,各治疗组小鼠一般状态改善,体重增长量升高,结肠黏膜上皮细胞核染色较均匀,细胞内线粒体等增生肿胀情况改善,c-jun、c-fos、c-myc蛋白及基因表达降低,p53、RB1蛋白及基因表达升高,以G、Z和Y组最为显著(P<0.01,P<0.05)。葛花解酲汤可能通过抑制原癌基因c-jun、c-fos、c-myc的激活,促进抑癌基因p53、RB1的表达,调控细胞增殖与凋亡,延缓炎-癌转化进程,修复受损的结肠黏膜组织,预防UCAC的发生。
To investigate the effect of Gehua Jiecheng Decoction on the expression of related pro-tumor suppressor genes in mice colon tissue of the"inflammation-cancer transformation"about ulcerative colitis(UC)-ulcerative colitis associated carcinogenesis(UCAC)with spleen deficiency and damp heat syndrome.Among 80 SPF C57BL/6 male mice,10 were randomly selected as blank group(group K),and the other 70 were set up to build the spleen deficiency damp-heat model.After the establishment of spleen deficiency damp-heat model,they were randomly divided into model 1,2,3 cycle group(M1,M2,M3),high,middle,low dose Gehua Jiecheng Decoction group(G,Z,D)and positive control mesalazine group(Y),10 cases in each group.The"inflammation-cancer transformation"about UC-UCAC was further established by azoxymethane(AOM)/dextran sodium sulfate(DSS).Each group was treated with corresponding drugs and the course of treatment was 4 weeks.Then to observed the general condition of mice,counted the body weight of mice,observed the ultrastructure of colonic mucosa under electron microscope,and detected the expression of c-jun,c-fos,c-myc,p53 and RB1 proteins and genes in mouse colon tissues by WB and RT-qPCR,respectively.Compared with the group K,the group M3 mice were in a worse general condition,body weight gain were significantly lower(P<0.01),the colonic mucosal epithelial cell nuclear staining were not uniform,the intracellular mitochondria showed a large amount of hyperplasia and swelling,and the proteins and genes expression of c-jun,c-fos and c-myc were significantly higher(P<0.01).The proteins and genes expression of p53 and RB1 were significantly lower(P<0.01).Compared with the group M3,the general condition of treatment group mice were improved,body weight gain were higher,colonic mucosa epithelial nuclei were relatively uniform,the mitochondria in cells hyperplasia swelling improvements,the proteins and genes expression of c-jun,c-fos and c-myc were lower.The proteins and genes expression of p53 and RB1 were higher.Groups G,Z and Y were in the most significant level(P<0.01,P<0.05).Gehua Jiecheng Decoction may can inhibit the expression of proto-oncogenes c-jun,c-fos and c-myc,promote the expression of tumor suppressor genes p53 and RB1,regulate cell proliferation and apoptosis,delay the process of inflammation-cancer transformation,repair the damaged colonic mucosa tissue,and prevent the occurrence of UCAC.