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

在Balb/c和心脏特异性SOCS3敲除小鼠（SOCS3- cko）中腹腔注射脂多糖（LPS）。注射LPS后，SOCS3-CKO小鼠的存活率高于WT小鼠。注射LPS后，SOCS3-CKO小鼠左室射血分数（LVEF）恢复到基线水平。SOCS-CKO小鼠心肌细胞中DHE阳性细胞减少。SOCS3-CKO小鼠注射LPS后STAT3磷酸化的持续时间和强度大于WT小鼠。SOCS3-CKO小鼠Bcl-xL表达增加，cleaved caspase3表达减少，细胞色素c释放减少。SOCS3-CKO小鼠在LPS注射后可阻止氧磷复合物iii的消耗。我们发现，注射LPS后，SOCS3-KO心脏中超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、硫氧还蛋白还原酶、过氧化物硫氧还蛋白等多种抗氧化基因的表达明显上调。我们的数据表明，心肌细胞中SOCS3的缺失通过增加STAT3信号和稳定线粒体来防止lps诱导的小鼠左室功能障碍。

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.