miR-21介导肠上皮细胞凋亡维持肠道稳态参与溃疡性结肠炎相关癌变研究

发布时间：2018-05-26 01:33

本文选题：miR- + 肠上皮细胞凋亡　；参考：《安徽医科大学学报》2017年04期

【摘要】：目的观察溃结癌变小鼠结肠黏膜miR-21、Caspase-8、肠上皮细胞凋亡及β-防御素表达,探讨溃结相关癌变的可能发病机制。方法 40只雄性清洁级Balb-c小鼠按体质量随机分2组即正常组和模型组,其中正常组10只,模型组30只。采用二甲肼/葡聚糖硫酸钠(DMH/DSS)复合法制备溃结癌变相关模型,造模30周结束后处死全部小鼠,应用光镜检测小鼠结肠黏膜组织形态学变化,电镜检测超微组织结构及上皮细胞凋亡变化;应用现代分子生物学技术检测miR-21、Caspase-8及β-防御素表达变化。结果与正常组比较,溃结相关癌变小鼠结肠黏膜光镜下见结肠黏膜不同程度缺损,表面渗出及坏死物,细胞形态异型,呈浸润癌改变;电镜下见肠黏膜层上皮细胞表面微绒毛稀疏,长短不一,细胞连接间隙增宽,见大量上皮细胞凋亡小体及细胞自噬,线粒体肿胀,结构不清,嵴结构消失,造模成功率约70%。与正常组比较,溃结癌变小鼠结肠黏膜miR-21、Caspase-8、β-防御素蛋白及mRNA表达均呈明显上升趋势,差异有统计学意义(P0.05)。结论溃结相关癌变的发生及发展可能是由于溃疡性结肠炎(UC)炎症持续,诱导miR-21、Caspase-8及β-防御素表达增加,破坏肠道免疫平衡,导致肠黏膜通透性增加,肠上皮细胞凋亡凋亡/自噬加剧,造成恶性循环,进一步破坏肠道稳态,上皮细胞异型增生,甚则癌变。
[Abstract]:Objective to investigate the expression of 尾 -defensin and miR-21 caspase-8 in colonic mucosa of mice with degenerative carcinogenesis and to explore the possible mechanism of carcinogenesis. Methods 40 male clean grade Balb-c mice were randomly divided into two groups according to their body weight: normal group and model group, including 10 normal mice and 30 model group. DSS / DMH / DMH / DMH / DSS composite method was used to establish the model of degeneration and carcinogenesis. All the mice were killed at the end of 30 weeks. The morphologic changes of colonic mucosa of the mice were detected by light microscope. Ultrastructure and apoptosis of epithelial cells were detected by electron microscope and the expression of miR-21 Caspase-8 and 尾 -defensin were detected by modern molecular biology technique. Results compared with the normal group, colonic mucosal defect, surface exudation and necrosis, cell morphology and invasive carcinoma were observed under light microscope in mice with ulceration associated carcinogenesis. Under the electron microscope, the microvilli on the surface of the epithelial cells of the intestinal mucosa were sparse and varied in length, and the gap between the junctional cells was widened. A large number of apoptotic bodies and autophagy of the epithelial cells were found, the mitochondria were swollen, the structure was not clear, the crest structure disappeared, and the success rate of modeling was about 70%. Compared with the normal group, the expression of miR-21 Caspase-8, 尾 -defensin protein and mRNA in colonic mucosa of mice with degenerative carcinogenesis showed an obvious upward trend, and the difference was statistically significant (P 0.05). Conclusion the occurrence and development of ulcerative node associated carcinogenesis may be due to the persistent inflammation of ulcerative colitis, which induces an increase in the expression of miR-21 Caspase-8 and 尾 -defensin, disrupts the intestinal immune balance and leads to an increase in intestinal mucosal permeability. Apoptosis / autophagy of intestinal epithelial cells increased, resulting in a vicious cycle, further destruction of intestinal homeostasis, epithelial dysplasia, and even carcinogenesis.
【作者单位】：海南省中医院消化科;广西中医药大学附属瑞康医院消化科;广西中医药大学第一附属医院;
【基金】：海南省卫生计生行业科研项目(编号:14A210219) 广西自然科学基金项目(编号:2013GXNSFAA019116)
【分类号】：R574.62

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