黄芪多糖对小鼠食管癌前病变的影响及机制研究  

Effect and mechanism of astragalus polysaccharides on precancerous lesions of esophagus in mice

作　　者：夏秀丽 赵树山 李云[1] 宋晓明[1] 徐珊[1] 程丽敏 李森 徐超[1] XIA Xiuli;ZHAO Shushan;LI Yun;SONG Xiaoming;XU Shan;CHENG Limin;LI Sen;XU Chao(Handan Central Hospital,Handan 056001,China)

机构地区：[1]邯郸市中心医院,河北邯郸056001

出　　处：《陕西中医》2022年第8期1003-1008,共6页Shaanxi Journal of Traditional Chinese Medicine

基　　金：河北省医学科学研究课题(20200457)。

摘　　要：目的:探讨黄芪多糖(APS)对小鼠食管癌前病变的影响及其作用机制。方法:将100只C57BL/6小鼠随机分为正常组26只、模型组26只、黄芪多糖组24只和全反式维甲酸组24只。除正常组外,其他组通过4-硝基喹啉-1-氧化物(4NQO)喂养15周诱导制备食管癌前病变小鼠模型。造模完成后,黄芪多糖组50 mg/kg灌胃给药,1次/d;全反式维甲酸组7.5 mg/kg灌胃给药,每2 d 1次;正常组和模型组灌胃给予0.9%氯化钠溶液,1次/d,共10周。HE染色法观察食管上皮组织病理学改变,透射电子显微镜观察食管上皮细胞超微结构改变;流氏细胞仪检测血液中CD3^(+)、CD4^(+)、CD8^(+)T细胞和NK细胞比例;RT-PCR法、Western blot法检测食管上皮组织信号传导和转录激活因子3(STAT3)、缺氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)mRNA和蛋白表达。结果:与正常组比较,模型组小鼠食管上皮组织呈现癌前病变或癌变,癌变率66.67%;食管上皮细胞可见胞核大小不等、核分裂相增多等超微结构改变;血液中CD3^(+)、CD4^(+)T细胞和NK细胞比例降低,CD4^(+)/CD8^(+)比值降低,CD8^(+)T细胞比例升高(P<0.05);食管上皮组织STAT3、HIF-1α、VEGF mRNA和蛋白表达量均升高(P<0.05)。与模型组比较,黄芪多糖组和全反式维甲酸组癌变率降低(P<0.05);上皮细胞超微结构改变明显改善;CD3^(+)、CD4^(+)T细胞和NK细胞比例均升高,CD4^(+)/CD8^(+)比值升高,CD8^(+)T细胞比例降低(P<0.05);STAT3、HIF-1α、VEGF mRNA和蛋白表达量均降低(P<0.05)。黄芪多糖组对各指标的调控作用均优于全反式维甲酸组(P<0.05)。结论:黄芪多糖对小鼠食管癌前病变进展具有抑制作用,可能与提高细胞免疫功能及抑制STAT3、HIF-1α、VEGF转录表达有关。Objective:To investigate the effect of astragalus polysaccharide(APS)on mouse esophageal precancerous lesions and its mechanism.Methods:A total of 100 C57BL/6 mice were randomly divided into normal group(n=26),model group(n=26),APS group(n=24)and all-trans retinoic acid(ATRA)group(n=24).Except for the normal group,the mice in other groups were induced by 4-Nitroquinoline 1-Oxide(4NQO)for 15 weeks to prepare mice models with esophageal precancerous lesions.After the modeling was completed,the mice in APS group were intragastrically administered with 50 mg/kg once a day;the mice in ATRA group were administered intragastrically with 7.5 mg/kg once every 2 days;the mice in normal group and model group were intragastrically administered with physiological saline once a day,10 weeks of treatment.The histopathological changes of esophageal epithelium was observe by HE staining.The ultrastructural changes of esophageal epithelial cells was observed by transmission electron microscope.The proportion of CD3^(+),CD4^(+),CD8^(+)T cells and natural killer(NK)cells in the blood were detected by flow cytometer.The mRNA and protein expression of signal transduction and activator of transcription factor 3(STAT3),hypoxia-inducible factor 1α(HIF-1α),vascular endothelial growth factor(VEGF)were detected by RT-PCR method and western blot method respectively.Results:Compared with the normal group,the esophageal epithelial tissue of the model group showed precancerous lesions or cancer,and the cancer rate was 66.67%.The ultrastructural changes such as the nucleus size was different,increased mitotic phase.The proportion of CD3^(+),CD4^(+)T cells and NK cells in the blood were decreased,the ratio of CD4^(+)/CD8^(+)was decreases,and the proportion of CD8^(+)T cells was increased(P<0.05).The mRNA and protein expression of STAT3,HIF-1α,VEGF were increased(P<0.05).Compared with the model group,the canceration rate of esophageal epithelial tissue in APS group and ATRA group was decreased(P<0.05);the ultrastructural changes of epithelial c

关 键 词：食管癌前病变 黄芪多糖 信号传导和转录激活因子3 缺氧诱导因子1Α 血管内皮生长因子 

分 类 号：R285.5[医药卫生—中药学]