High Mobility Group Box 1 Promotes Myocardial Damage And Influences CD4~+T,CD8~+T Cell And IL-17 Through Toll Like Receptor 4 In Ischemia Myocardial

Objective:C57BL/6 wild type?WT?mice and TLR4 knockout(TLR4^-/-)mice,and high-dose isoproterenol?ISO?was used to construct mouse acute MI model.?1?Changes of cardiac function,myocardial apoptosis,myocardial tissue necrosis,myocardial tissue fibrosisand,HMGB1 expression,CD4⁺T,CD8⁺T lymphocyte proportion and interleukin?IL?-17proportion in myocardial ischemia in mice were observed.?2?After administration of recombinant high mobility protein B1,the changes of cardiac function,myocardial apoptosis and CD4⁺T,CD8⁺T lymphocyte proportion and interleukin IL-17 proportion in myocardial ischemia were observed.Methods:?1?30 wild-type?WT?and 30 TLR4 knockout(TLR4^-/-)C57BL/6 mice were randomly divided into the control group,isoproterenol induced ischemia myocardial group?ISO?and ISO+rHMGB1 group.?2?This experiment used a mouse high-dose ISO?20mg/kg/day,continuous injection for seven days?to establish an acute myocardial ischemia model.WT mice and TLR4^-/-mice were randomly divided into the following groups of 10mice each.The Control group:intraperitoneal injection of 0.9%sodium chloride injection20mg/kg/day for 7 consecutive days;ISO group:20 mg/kg/day ISO for 7 consecutive days of intraperitoneal injection;ISO combination+HMGB1?recombinan HMGB1,rHMGB1?group:mice were given intraperitoneal injection of 10?g/kg of rHMGB1 12 h before induction of MI injury.?3?Cardiac function,myocardium histopathological changes and myocardial apoptosis index were evaluated by echocardiography,HE,sirius red staining,and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling?TUNEL?,Myocardial tissue HMGB1 was detected by immunohistochemistry.Flow cytometry was applied to detect the proportion CD4⁺T,CD8⁺T cells,and IL-17 of spleen.Results:?1?Compared to the control group,ISO group caused cardiac function impairment,myocardial tissue necrosis and fibrosis,cardiomyocyte apoptosis,increased expression of HMGB1,elavated CD4⁺T cells proportion and IL-17 proportion,and CD4⁺/CD8⁺ratio in vivo?P<0.05?.?2?Compared to the ISO group,ISO+rHMGB1 group had worse cardiac function,myocardial tissue necrosis and fibrosis,cardiomyocyte apoptosis,increased expression of HMGB1,higher CD4⁺T cells proportion and IL-17 proportion,and CD4⁺/CD8⁺ratio in vivo?P<0.05?.?3?Compared to the WT-ISO group,TLR4^-/--ISO group had better cardiac function,alleviative myocardial tissue necrosis and fibrosis,cardiomyocyte apoptosis,reduced proportion of HMGB1,lower CD4⁺T cells proportion and IL-17 proportion,and CD4⁺/CD8⁺ratio in vivo?P<0.05?.?4?Compared to the WT-ISO+rHMGB1 group,TLR4^-/--ISO+rHMGB1 group had better cardiac function,alleviative myocardial tissue necrosis and fibrosis,cardiomyocyte apoptosis,reduced expression of HMGB1,lower CD4⁺T cells proportion and IL-17 proportion,and CD4⁺/CD8⁺ratio in vivo?P<0.05?.Conclusion:1.rHMGB1 can aggravate myocardial ischemic injury through toll like receptor 4.2.During myocardial ischemia,the HMGB1/TLR4 signaling pathway may be involved in the regulation of CD4⁺T cells,CD8⁺T cells,and IL-17.