镉对果蝇肠道上皮细胞损伤和调控中肠干细胞增殖、分化机制的研究  

Research on Effects of Cadmium Induced Intestinal Epithelial Cell Injury and Regulation on Intestinal Stem Cells Regeneration and Differentiation in Drosophila Mid-gut

作　　者：楼哲丰[1] 曹琼洁[1] 冯钰淇[1] 蔡慧敏[1] 段银波[1] 张岩[2] 林鑫华[2] 金龙金[1] 

机构地区：[1]温州医学院检验医学院,生命科学学院,浙江省医学遗传学重点实验室,温州325035 [2]中国科学院动物研究所生物膜与膜生物工程国家重点实验室,北京100101

出　　处：《中国细胞生物学学报》2013年第5期602-608,共7页Chinese Journal of Cell Biology

基　　金：温州医学院科研基金重大项目(批准号:XNK07005);温州市科技局计划项目(批准号:Y20110030)资助的课题~~

摘　　要：重金属元素镉具有较强的生物毒性,是威胁人类健康的重要环境污染物质。为探索镉的过量摄入对生物消化系统的潜在影响,以果蝇中肠系统为实验模型,以不同浓度的氯化镉作为处理因素,探讨其对肠道细胞的损伤作用和调控中肠干细胞增殖、分化的相应机制。通过透射电镜观察,发现镉对果蝇中肠上皮细胞超微结构具有损伤作用,并且损伤程度具有显著的浓度依赖性;免疫荧光结果证实,镉的过量摄入对中肠干细胞(intestinal stem cell,ISC)、成肠细胞(enteroblast,EB)和肠上皮细胞(enterocyte,EC)的数量和比例能够产生影响,且显著促进中肠干细胞的增殖;Real-time RT-PCR检测结果表明,肠道组织中表皮生长因子受体(epidermal growth factor recep-tor,EGFR)和JAK/STAT信号通路配体基因的转录水平显著提高,JAK/STAT信号通路同时被大幅度活化。结果显示:高浓度镉的摄入对果蝇中肠上皮细胞核膜、线粒体和微绒毛等超微结构造成损伤,该类损伤能够诱使果蝇肠道组织上调表达相关配体蛋白,从而激活干细胞的EGFR和JAK/STAT信号通路,从而促进ISC的增殖与分化能力,继而实现对肠道损伤组织进行及时的修复。然而,中肠干细胞增殖信号通路的持续激活以及干细胞的过度增殖同样具有诱发肠道肿瘤发生的潜在可能。Cadmium is health in environment. To explore adult mid-gut, which is proved an a typical toxic heavy metal element, which is extremely harmful for people＇s the harmful mechanism of cadmium in digestive system, we use the Drosophila excellent model to study tissue damage and intestinal stem cell （ISC） regulationmechanisms. In this work, the flies were fed with different concentrations of cadmium chloride. Cadmium over intake could induce ultra-structural damage in mid-gut epithelial cells, especially the nuclear membrane, mitochon- drion and microvilli. The level of damage is directly depending on the concentrations of cadmium used. Immuno- fluorescence studies show that the number and proportion of ISC, enteroblast （EB）, enterocyte （EC） are varied among different cadmium feeding groups, as cadmium could up-regulate the proliferation and differentiation ability of ISC. Real-time RT-PCR data demonstrate that cadmium treatment induces over-expression of epidermal growth factor receptor （EGFR） and JAK/STAT ligands in fly guts. All our results demonstrated that mid-gut epithelial cell damaged by cadmium treatments were mainly manifested by nuclear membrane blurring or wrinkle, mitochondrial swelling, vacuolization, hetero-pyknosis and intestinal microvilli defects. And the ultra-structural damaged in ECs could up-regulate the expression of EGFR and JAK/STAT signaling ligands, which promoted ISC proliferation and differentiation. Thus the gut regenerates through refurnishing the damaged ECs by newly differentiated cells from ISCs. So, this mechanism enables digestive system to adapt the toxic environmental heavy metals, like cadmium. However, overactivation of these signaling pathways could also lead to potential tumorigenesis in gut.

关 键 词：镉 果蝇 超微结构损伤 中肠 干细胞 

分 类 号：Q25[生物学—细胞生物学]