| Objective Acute myocardial infarction(AMI)has always been a worldwide threat to human life and health.Once myocardial infarction(MI)occurs,how to treat and prevent adverse complications is still unsolved.Thymic stromal lymphopoietin(TSLP)is involved in the course of a variety of human diseases,including allergic diseases,chronic inflammatory diseases and tumors,and plays a role in inflammatory regulation and organ fibrosis,but its role in cardiovascular diseases has been little studied.The purpose of this study was to investigate the effects ofTSLP/TSLPR on cardiac function and ventricular remodeling after myocardial infarction.Method(1)The genetic phenotype of Crlf2-/-mice(TSLPR knockout mice)was assessed by PCR and agarose gel electrophoresis.(2)MI was induced in 8-week Crlf2-/-mice and the wild-type C57BL/6 mice at about8 weeks by the ligation of the left anterior descending branch of the coronary artery.In sham-operated mice,the same procedures with ligation were performed.On the 14 th day after the operation,left ventricular ejection fraction(EF),left ventricular fractional shortening(FS),left ventricular end-diastolic volume(LVEDV)and left ventricular end-systolic volume(LVESV)were evaluated with echocardiography using both LV Trace method and Simpson method,so as to compare cardiac function between experimental groups.(3)C57BL/6 mice were randomly divided into7 groups,the former two groups are respectively blank control group and negative control group with jugular vein injection of PBS,100 ul per mouse,the other five groups are treated with jugular vein injection of AAV9-c Tn T-m TSLP virus carriers,100 ul per mouse,which can specifically express TSLP protein in cardiomyocyte,with different doses of 1,3,5,7,9* 10^11vg per mouse.3 weeks later,TSLP protein expression in mice heart was measured with western blot.(4)C57BL/6 mice were randomly divided into the following groups: 1)the TSLP-overexpressed group: the overexpressing TSLP virus vectors were injected into the jugular vein 2-3weeks before MI,and the dose was set at 5*10^11vg per mouse;2)negative control group: 100 ul PBS per mouse was injected into the jugular vein 2-3weeks before MI;3)sham operation group.Echocardiography was performed on all mice on the 14 th day after MI,and EF,FS,LVEDV and LVESV values were measured by LV Trace method and Simpson method respectively toevaluate the cardiac function.Result(1)The knockout of TSLPR gene were confirmed in Crlf2-/-mice.(2)The echocardiography measured by LV Trace method and Simpson method indicated that,compared with sham group,the cardiac function of wild-type mice and Crlf2-/-mice in the MI group significantly deteriorated,with decreased EF and FS values and increased LVEDV and LVESV values.Compared with wild-type MI mice,the cardiac function of Crlf2-/-MI mice further deteriorated,with a significant decrease in EF value and a great increase in LVESV value suggested by both the LV Trace method and Simpson method,and a significant increase of LVEDV value suggested by the Simpson method.(3)Jugular vein injection of AAV9-c Tn T-m TSLP virus resulted in dose-dependent upregulation of TSLP in heart and the appropriate dose of AAV9-c Tn T-m TSLP virus vector was5*10^11vg per mouse.(4)The echocardiography measured by LV Trace method and Simpson method indicated that,compared with sham group,EF and FS values of wild-type mice and TSLP-overexpressed mice in MI group decreased,LVEDV and LVESV values increased,and the cardiac function significantly deteriorated.Compared with wild-type MI mice,there was no significant change in cardiac function of TSLP-overexpressed MI mice,with only a slight increase in EF value,and no significant changes in FS,LVEDV,and LVESV values.Conclusion(1)TSLPR knockout resulted in obvious deterioration of cardiac function in MI mice,suggesting the protective role of TSLP in the condition.(2)Cardiac overexpression of TSLP failed to show a protective effect in MI mice. |
PDF Full Text Request