卡博替尼抵抗产单核细胞李斯特菌感染的体内实验研究

Experimental study on cabozantinib against infection caused by Listeria monocytogenes in mice

目的探究卡博替尼抗产单核细胞李斯特菌(Listeria monocytogenes,LM)感染的作用。方法 24只6周龄C57BL/6小鼠随机分为不同剂量卡博替尼组,每组6只,腹腔注射LM菌液后,分别灌胃给予0,10,15,20μg/g卡博替尼,比较四组小鼠肝脾细菌载量。另将6周龄C57BL/6小鼠随机分为卡博替尼组、氨苄青霉素(Ampicillin,Amp)组、卡博替尼和Amp联合用药组以及PBS对照组,腹腔注射LM菌液后,分别灌胃给予卡博替尼20μg/g、腹腔注射氨苄青霉素20μg/g、灌胃卡博替尼20μg/g后腹腔注射20μg/g氨苄青霉素、以及腹腔注射等量PBS,比较四组小鼠的生存曲线、肝脾细菌载量以及肝脏病理改变。结果随着卡博替尼剂量增加,肝脾细菌载量逐渐降低,其中20μg/g剂量组相比PBS组,肝脾细菌载量显著降低(P<0.01);卡博替尼单独用药组小鼠相比PBS对照组小鼠,生存率较高、肝脏和脾脏的细菌载量较低(P<0.05)、肝脏炎症病变程度轻,联合用药组比卡博替尼单独用药组小鼠的肝脾细菌载量均显著降低(P<0.05)。结论体内实验研究结果提示卡博替尼具有抵抗产单核细胞李斯特菌感染的作用。

Objective To explore the effect of cabozantinib on the infection of Listeria monocytogenes（ LM）. Methods The 24 6-week-old mice（ C57 BL/6） were randomized into four groups（ n = 6 each） and treated with 0,10,15,20 μg/g cabozantinib by intragastric injection after intraperitoneal injection of LM,respectively,and then the bacterial counts in liver and spleen were compared among four groups. The 6-week-old mice were randomized into cabozantinib group,ampicillin（ Amp） group,combination group and PBS control group,and were respectively treated with cabozantinib（ 20 μg/g） by intragastric injection,Amp（ 20 μg/g） by intraperitoneal injection,cabozantinib in combination with Amp,and equal PBS by intraperitoneal injection after intraperitoneal injection of LM. And then the survival curve,the number of bacteria in liver and spleen and pathological changes of liver tissue were compared. Results The bacterial load in liver and spleen was decreased gradually with the increase of cabozantinib. And the bacteria load in liver and spleen was lower in 20 μg/g cabozantinib group than in PBS group（ P〈0. 01）. The survival rate was higher and the bacterial load in liver and spleen was lower in 20 μg/g cabozantinib group than in PBS group（ P〈0. 05）,and the pathological changes was lighter. The bacterial load in liver and spleen in combination group was lower than that in cabozantinib group（ P〈0. 05）. Conclusion The vivo experiment indicates that cabozantinib could resist the infection of LM.