基于miRNA-146a介导IRAK1/TRAF6/NF-κB通路探讨益气温阳法调控脓毒症大鼠心肌细胞凋亡的作用机制

脓毒症常诱发脓毒症心功能障碍(SIMD)，导致死亡率明显增加。而心肌细胞凋亡是导致SIMD的主要机制之一。TNF-α通过激活caspase-3介导心肌细胞凋亡，而TNF-α主要受IRAK1/TRAF6/NF-κB炎症通路调控。.脓毒症表现为阳气虚衰、心阳不振。我们研究发现，参附注射液益气温阳，能改善脓毒症心功能障碍，且可诱导miRNA-146a表达抑制IRAK1/TRAF6/TNF-α炎症通路。.因此我们提出假说：参附注射液改善脓毒症心功能基于miRNA-146a介导IRAK1/TRAF6/NF-κB炎症通路调控caspase-3表达，抑制脓毒症大鼠心肌细胞凋亡。.本课题通过miRNA-146a基因转染、抑制物转染和心肌细胞培养，验证参附注射液基于miRNA-146a介导IRAK1/TRAF6/NF-κB调控细胞凋亡因子caspase-3，探讨其作用机制.

Sepsis often induces sepsis-induced cardiac dysfunction (SIMD), which leads to a significant increase in mortality. Cardiomyocyte apoptosis is one of the main mechanisms of SIMD. TNF-α mediates cardiomyocyte apoptosis by activating caspase-3, and TNF-α is mainly regulated by IRAK1/TRAF6/NF-κB inflammatory pathway..Sepsis is characterized by deficiency of Yang Qi and failure of heart Yang. We found that Shenfu injection can induce miRNA-146a expression which can inhibit IRAK1/TRAF6/NF-κB inflammatory pathway..Therefore, we propose the hypothesis that Shenfu injection can regulate the expression of Caspase-3 and inhibit the apoptosis of myocardial cells in sepsis rats based on miRNA-146a mediated IRAK1/TRAF6/NF-κB inflammatory pathway..Through miRNA-146a gene transfection, inhibitor transfection and cardiomyocyte culture, this study verified that Shenfu injection based on miRNA-146a mediated IRAK1/TRAF6/NF-κB regulated apoptosis factors caspase-3, and explored the key mechanism of Shenfu Injection in treating SIMD and regulating apoptosis.