【Animal Experiment】-Experimental study of Cabotinib blocking Listeria monocytogenes infection in mice

  OBJECTIVE: To explore the possibility of the c-Met receptor tyrosine kinase inhibitor cabozantinib as a new type of drug against Listeria monocytogenes (LM) infection.

   Method: 6-week-old C57BL/6 mice were randomly divided into cabozantinib group, ampicillin (Amp) group, cabozinib and ampicillin combination group and PBS control group. After intraperitoneal injection of LM bacteria solution, intragastric administration of 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 given to compare 4 groups Survival curve of mice, 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. Results: Compared with the control group, the cabozantinib group had a higher survival rate, and significantly reduced the bacterial load in blood and brain tissue (P<0.05, P<0.001); serum IL-10 and NF-κB p65 levels were significantly reduced (P <0.05, P<0.01); the amount of EB in brain tissue decreased (P<0.001), and the pathological changes of brain tissue were alleviated. The blood and brain bacterial load of mice in the combined treatment group with bicarbostinib alone (P<0.001), serum IL-10 and NF-κB p65 content (P<0.01, P<0.001), brain tissue EB content All were significantly reduced (P<0.001).

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