The molecular mechanism of cardiomyocyte protection against LPS-induced heart failure-From the regulation of cytokine signaling

给Balb/c和心脏特异性SOCS3基因敲除小鼠(SOCS3-CKO)腹腔注射脂多糖(LPS)。注射内毒素后，SOCS3-CKO小鼠的存活率明显高于WT小鼠。注射脂多糖后，SOCS3-CKO小鼠的左心室射血分数(LVEF)恢复到基线水平。SOCS-CKO小鼠心肌细胞DHE阳性细胞减少。SOCS3-CKO小鼠注射脂多糖后STAT3磷酸化的持续时间和强度均大于WT小鼠。SOCS3-CKO小鼠bclxl表达增加，caspase3裂解表达减少，细胞色素c释放减少。SOCS3-CKO小鼠可防止注射脂多糖后OXPHOS复合体的耗竭。我们发现，注射脂多糖后，超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、硫氧还蛋白还原酶、过氧化硫氧还蛋白等多种抗氧化剂基因在SOCS3-KO心脏的表达明显上调。我们的数据表明，心肌细胞中SOCS3基因的缺失可以通过增强STAT3信号通路和稳定线粒体来预防脂多糖诱导的小鼠左心功能障碍。

Lipopolysaccharide(LPS) was injected intraperitoneally in Balb/c and cardiac-specific SOCS3 knockout mice(SOCS3-CKO). SOCS3-CKO mice showed greater survival rate than WT mice after LPS injection. Left ventricular ejection fraction(LVEF) was restored to the baseline in SOCS3-CKO mice after LPS injection. DHE positive cells in cardiomyocytes were reduced in SOCS-CKO mice. The duration and intensity of STAT3 phosphorylation after LPS injection was greater in SOCS3-CKO mice than WT mice. Bcl-xL expression was increased and cleaved caspase3 expression and cytochrome c release were decreased in SOCS3-CKO mice. SOCS3-CKO mice prevents the depletion of Oxphos complexesIandIIIafter LPS injection. We found that expressions of multiple antioxidants genes including superoxide dismutases, catalase, glutathione peroxidase, thioredoxin reductase, peroxide thioredoxin were markedly upregulated in SOCS3-KO hearts after LPS injection. Our data show that the deletion of SOCS3 in cardiomyocytes prevents the LPS-induced LV dysfunction in mice via augmenting the STAT3 signaling and stabilizing mitochondria.