The Effect Of AMG487 Regulating The Expression Of CXCL10/CXCR3 On Coronary Artery And Myocardium Of Kawasaki Disease Model Mice

Objective: In order to explore the effect of inhibiting the expression of CXCL10/CXCR3 with AMG487 on coronary artery and myocardial injury in KD mice,and to find out its possible mechanism,providing new ideas and methods for the treatment of coronary artery and myocardial injury in KD mice.Methods: Nine C57BL/6 male mice aged 6-8 weeks were randomly divided into the following three groups(n=3): control group,KD group,KD+AMG487 group;First,the model mice of coronary arteritis induced by intraperitoneal injection of Lactobacillus casei cell wall extract(LCWE)were constructed.The KD+AMG487 group started intraperitoneal injection of AMG487(5mg/kg,once every 48h)on the second day after injection of LCWE.The control group and KD group were injected with the same volume of PBS.The mice were euthanized for two consecutive weeks and 14 days later.The myocardial tissue and serum were collected for the following tests: 1.The expression level of CXCL10,CXCR3,TNF-α and IL-1β in serum and myocardial tissue of each group mice was measured by ELISA;2.The expression level of JAK2 and STAT3 in myocardial tissue of mice in each group was measured by Western-Blot technique.3.The tissue samples(myocardial tissue,coronary artery)were stained with HE to observe the changes of tissue structure and the infiltration of inflammatory cells around them;4.Statistical analysis: Graphpad Prism 8.0 software is used for data statistical analysis and drawing.Results: 1.The expression level of CXCL10 in serum and myocardial tissue of KD group mice was significantly higher than that of control group mice(P<0.001);The application of AMG487 could reduce the expression of CXCL10 in serum and tissue of KD mice,and the difference was statistically significant(P<0.05);2.The expression level of CXCR3 in serum and myocardial tissue of KD group mice was significantly higher than that of control group mice(P<0.001);After the application of AMG487,the expression of CXCR3 in serum and myocardial tissue of KD mice decreased significantly(P<0.05);3.The expression level of IL-1β in serum and myocardial tissue of KD mice increases higher compared with the control group(P<0.05),the expression of TNF-α in serum and myocardial tissue of KD group mice was significantly higher(P<0.05)compared with the control group,AMG487 can reduce TNF-α in myocardial tissue of KD mice,but the difference was not significant(P>0.05);4.Compared with the control group,the expression level of JAK2 and STAT3 in the myocardium of KD group mice increased;The expression of AMG487 decreased significantly after treatment(P<0.05);5.More inflammatory cells,including lymphocytes and neutrophils,were found in the coronary artery and myocardial tissue of mice in KD group,the infiltration of inflammatory cells decreased after the application of AMG487.Conclusion: 1.CXCL10/CXCR3 activates JAK2/STAT3 pathway to participate in the occurrence of coronary artery and myocardial injury in KD;2.AMG487 can inhibit the expression of CXCL10/CXCR3 in mice and reduce the inflammatory damage of myocardium and coronary artery in KD model mice.