本文選題：卡博替尼　切入點：產(chǎn)單核細胞李斯特菌　出處：《南方醫(yī)科大學學報》2016年02期 　論文類型：期刊論文

【摘要】：目的探討c-Met受體阻斷劑卡博替尼(Cabozantinib,XL-184)能否抑制產(chǎn)單核細胞李斯特菌(Listeria monocytogenes,LM)進入Caco-2細胞并降低對細胞的損傷。方法通過侵襲實驗研究XL-184在抑制LM進入Caco-2細胞中的作用,并研究劑量及時間與侵襲率的關(guān)系;Caco-2細胞種植于Transwell上室,LM感染單層Caco-2細胞,然后在上室中加入辣根過氧化物酶(HRP),通過測定跨上皮細胞電阻(TEER)值及計數(shù)從上室滲透到下室的LM數(shù)量和HRP濃度,預測X-184對單層細胞通透性的保護作用;檢測乳酸脫氫酶(LDH)釋放水平推測細胞膜的滲透性;熒光染色鑒定細胞活性。結(jié)果相比對照組,侵襲實驗顯示,XL-184處理組的LM侵襲率明顯降低(P=0.000),且侵襲率隨XL-184濃度和作用時間的增加而顯著降低,聯(lián)合用藥效果優(yōu)于單獨用藥(P0.05)。細胞通透性實驗表明,XL-184可明顯抑制LM誘導的跨上皮細胞電阻(TEER)的降低(P0.05),并可降低辣根過氧化物酶和細菌介導的細胞通透性(P=0.000);細胞活性實驗表明,XL-184可提高細胞存活率(P0.01);同時,可顯著降低LM誘導的LDH釋放(P0.05)。結(jié)論 XL-184可能在抑制LM侵襲Caco-2及降低LM誘導的Caco-2損傷中起重要作用。因此,XL-184有望成為潛在的治療和預防李斯特菌感染的有效藥物。
[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.
【作者單位】： 南方醫(yī)科大學公共衛(wèi)生與熱帶醫(yī)學學院//廣東省熱帶病研究重點實驗室微生物學系;南方醫(yī)科大學第一臨床醫(yī)學院;
【基金】：廣州市科技計劃(2014J4100145) 2015年度國家級和省級大學生創(chuàng)新創(chuàng)業(yè)訓練計劃項目(201512121026)
【分類號】：R378

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