南方医科大学学报 ›› 2016, Vol. 36 ›› Issue (01): 56-.

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卡博替尼阻断小鼠体内产单核细胞李斯特菌感染的实验研究

肖晴,何肖龙,张文炳,罗军,龙敏,曹虹   

  • 出版日期:2016-01-20 发布日期:2016-01-20

Cabozantinib inhibits Listeria monocytogenes infection in mice

  • Online:2016-01-20 Published:2016-01-20

摘要: 目的探讨c-Met受体酪氨酸激酶抑制剂卡博替尼作为抗产单核细胞李斯特菌(Listeria monocytogenes, LM)感染新型药物
的可能性。方法6周龄C57BL/6小鼠随机分为卡博替尼组、氨苄青霉素(Amp)组、卡博替尼和氨苄青霉素联合用药组和PBS
对照组。腹腔注射LM菌液后,再分别灌胃给予卡博替尼20 μg/g、腹腔注射氨苄青霉素20 μg/g、卡博替尼和氨苄青霉素联合用
药、以及腹腔注射等量PBS,比较4组小鼠的生存曲线、血液和脑组织细菌载量、血清IL-10和脑脊液中NF-κB p65含量、脑组织
中依文思蓝(EB)含量以及脑组织病理变化。结果卡博替尼组比对照组小鼠生存率增高、血液和脑组织的细菌载量明显减少
(P<0.05,P<0.001);血清IL-10和NF-κB p65含量显著降低(P<0.05,P<0.01);脑组织EB量降低(P<0.001),脑组织病理变化减
轻。联合用药组比卡博替尼单独用药组小鼠血液和脑细菌载量(P均<0.001)、血清IL-10和NF-κB p65含量(P<0.01,P<0.001)、
脑组织EB量均明显减少(P<0.001)。结论酪氨酸激酶抑制剂卡博替尼对LM感染具有阻断作用,为研发新型抗胞内感染药物
提供重要理论依据。

Abstract: Objective To test the effect of the c-Met inhibitor cabozantinib in inhibiting infections by Listeria monocytogenes (LM)
in mice. Methods C57BL/6 mice at 6 weeks of age were subjected to intraperitoneal injection of LM and randomized into 4
groups for treatment with intraperitoneal injection of PBS, intragastric administration of cabozantinib (20 μg/g), intraperitoneal
injection of ampicillin (Amp, 20 μg/g), or cabozantinib plus Amp. The survival curves were drawn for each group, and the
number of bacteria in the blood and brain tissues was determined; serum IL-10 level and NF-κB p65 level in the cerebrospinal
fluid (CSF) were assayed, and Evans Blue (EB) content and pathological changes in brain were examined. Results Compared
with PBS-treated mice, the mice treated with cabozantinib showed a significantly higher survival rate, lower bacterial counts in
the blood and brain (P<0.05 or 0.001), lower IL-10 (P<0.05) and NF-κB p65 levels (P<0.01), lower brain EB content (P<0.001), and
milder pathological changes in the brain. The blood and brain bacterial counts (P<0.001), IL-10 (P<0.01) and NF-κB p65 levels
(P<0.001), and brain EB content (P<0.001) were all significantly lower in mice treated with the combination of drugs than in
mice treated with cabozantinib alone. Conclusion Cabozantinib can inhibit LM infection in mice and has important values in
developing new anti-intracellular infection drug.