卡博替尼抑制产单核细胞李斯特菌侵袭Caco-2细胞的机制

发布时间：2018-03-15 11:38

本文选题：卡博替尼　切入点：产单核细胞李斯特菌　出处：《南方医科大学学报》2016年02期 　论文类型：期刊论文

【摘要】：目的探讨c-Met受体阻断剂卡博替尼(Cabozantinib,XL-184)能否抑制产单核细胞李斯特菌(Listeria monocytogenes,LM)进入Caco-2细胞并降低对细胞的损伤。方法通过侵袭实验研究XL-184在抑制LM进入Caco-2细胞中的作用,并研究剂量及时间与侵袭率的关系;Caco-2细胞种植于Transwell上室,LM感染单层Caco-2细胞,然后在上室中加入辣根过氧化物酶(HRP),通过测定跨上皮细胞电阻(TEER)值及计数从上室渗透到下室的LM数量和HRP浓度,预测X-184对单层细胞通透性的保护作用;检测乳酸脱氢酶(LDH)释放水平推测细胞膜的渗透性;荧光染色鉴定细胞活性。结果相比对照组,侵袭实验显示,XL-184处理组的LM侵袭率明显降低(P=0.000),且侵袭率随XL-184浓度和作用时间的增加而显著降低,联合用药效果优于单独用药(P0.05)。细胞通透性实验表明,XL-184可明显抑制LM诱导的跨上皮细胞电阻(TEER)的降低(P0.05),并可降低辣根过氧化物酶和细菌介导的细胞通透性(P=0.000);细胞活性实验表明,XL-184可提高细胞存活率(P0.01);同时,可显著降低LM诱导的LDH释放(P0.05)。结论 XL-184可能在抑制LM侵袭Caco-2及降低LM诱导的Caco-2损伤中起重要作用。因此,XL-184有望成为潜在的治疗和预防李斯特菌感染的有效药物。
[Abstract]:Objective to investigate whether c-Met receptor antagonist Cabozantinib (XL-1844) can inhibit the entry of Listeria monocytogenes LMinto Caco-2 cells and reduce the damage to Caco-2 cells. Methods the role of XL-184 in inhibiting LM entry into Caco-2 cells was studied by invasive experiments. The relationship between dose, time and invasion rate was studied. Caco-2 cells were implanted in Transwell LM-infected monolayer Caco-2 cells. Then horseradish peroxidase (HRP) was added to the upper chamber to predict the protective effect of X-184 on the permeability of monolayer cells by measuring the resistance of transepithelial cells and counting the number of LM infiltrating into the lower chamber from the upper chamber and the concentration of HRP. The release level of lactate dehydrogenase (LDH) was measured to speculate the permeability of cell membrane. Fluorescence staining was used to identify the cell activity. The invasion test showed that the invasion rate of LM in XL-184 group was significantly decreased with the increase of XL-184 concentration and action time, and the invasion rate was significantly decreased with the increase of XL-184 concentration and action time. The effect of combined use was better than that of P0.050.The cell permeability test showed that XL-184 could significantly inhibit the decrease of transepithelial cell resistance induced by LM (P0.05N), and could reduce horseradish peroxidase (HRP) and bacteria-mediated cell permeability (P0. 000) and cell viability. The sex experiment showed that XL-184 could improve cell survival rate (P0.01), and at the same time, Conclusion XL-184 may play an important role in inhibiting LM invasion of Caco-2 and reducing LM-induced Caco-2 damage. Therefore, XL-184 may be an effective drug for the treatment and prevention of Listeria sp. Infection.
【作者单位】：南方医科大学公共卫生与热带医学学院//广东省热带病研究重点实验室微生物学系;南方医科大学第一临床医学院;
【基金】：广州市科技计划(2014J4100145) 2015年度国家级和省级大学生创新创业训练计划项目(201512121026)
【分类号】：R378

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