动物造模 z-bio 2022-11-09 377

　　Objective: To investigate the possibility of cabozantinib, a c-Met receptor tyrosine kinase inhibitor, as a novel drug against Listeria monocytogenes infection.

　　Methods: 6-week-old C57BL/6 mice were randomly divided into cabozantinib group, ampicillin (Amp) group, cabozantinib and ampicillin combination group and PBS control group. After intraperitoneal injection of LM bacterial solution, cabozantinib 20 μg/g, intraperitoneal injection of ampicillin 20 μg/g, combination of cabozantinib and ampicillin, and intraperitoneal injection of the same amount of PBS were administered by intragastric administration, respectively. The four groups were compared. Survival curve, bacterial load in blood and brain tissue, serum IL-10 and NF-κB p65 content in cerebrospinal fluid, Evans blue (EB) content in brain tissue, and pathological changes in brain tissue of mice.

　　Results: Compared with the control group, the cabozantinib group had a higher survival rate, and the bacterial loads in the blood and brain tissues were significantly decreased (P<0.05, P<0.001); the serum IL-10 and NF-κB p65 levels were significantly decreased (P<0.05, P<0.001). <0.05, P<0.01); the amount of EB in brain tissue decreased (P<0.001), and the pathological changes in brain tissue were alleviated. The blood and brain bacterial loads of the mice in the combination group and the bicabotinib alone group (both P<0.001), serum IL-10 and NF-κB p65 contents (P<0.01, P<0.001), and the amount of EB in the brain tissue were significantly reduced (P<0.001).

　　Conclusion: The tyrosine kinase inhibitor cabozantinib has a blocking effect on LM infection, which provides an important theoretical basis for the development of new anti-intracellular infection drugs.