[HMGB1 promotes myocardial ischemic injury and regulates the proportion of CD4 + , CD8 + T cells and Th17 cells in spleen through TLR4].

Objective To elucidate how high-mobility group box 1 (HMGB1) exacerbates myocardial damage and infuences CD4+ , CD8+ and Th17 T lymphocytes of spleen through Toll like receptor 4 (TLR4) in ischemia myocardial injury. Methods 30 wild-type (WT) and 30 TLR4 knockout (TLR4-/- ) C57BL/6 mice were randomly divided into the control group, isoproterenol induced ischemia myocardial damage group (ISO) and ISO-rHMGB1 group. The cardiac function of mice was evaluated by echocardiography, and the pathological changes of myocardial tissue were observed by HE staining and Sirius red staining. The apoptosis index of myocardial cells was detected by TUNEL, and the proportion of CD4+ , CD8+ T cells and Th17 cells in spleen tissues was detected by flow cytometry. Results Compared with the control group, ISO treated mice showed cardiac function impairment, myocardial tissue necrosis and fibrosis, myocardial cell apoptosis, and increased the proportion of CD4+ T lymphocytes, CD4+ /CD8+ T ratio and Th17 cells in the spleen. Compared to the ISO group, cardiac function damage, myocardial tissue necrosis and fibrosis, and myocardial cell apoptosis were aggravated in the ISO combined rHMGB1 group, and the proportion of CD4+ T lymphocytes, CD4+ /CD8+ T ratio and Th17 cells in the spleen was higher. Compared with wild-type mice in the ISO combined rHMGB1 group, TLR4-/- mice in the ISO combined rHMGB1 group showed decreased cardiac function, myocardial tissue necrosis, fibrosis and myocardial cell apoptosis, and significantly reduced the proportion of CD4+ T lymphocytes, CD4+ /CD8+ T ratio and Th17 cells. Conclusion HMGB1 induces myocardial injury in myocardial ischemia through TLR4, and up-regulates the proportion of CD4+ T cells, CD4+ /CD8+ T ratio and Th17 cells in the spleen, which may promote myocardial inflammatory damage.