Toll-like receptor 9 promotes cardiac inflammation and heart failure during polymicrobial sepsis.

Toll-like receptor 9 promotes cardiac inflammation and heart failure during polymicrobial sepsis.
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DOI:
10.1155/2013/261049
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发表时间:
2013
影响因子:
4.6
通讯作者:
Boehm O
Boehm O
中科院分区:
医学3区
文献类型:
--
作者:
Lohner R;Schwederski M;Narath C;Klein J;Duerr GD;Torno A;Knuefermann P;Hoeft A;Baumgarten G;Meyer R;Boehm O

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背景目的是阐明Toll样受体9(TLR 9)在多微生物脓毒症小鼠模型心脏炎症和脓毒症心力衰竭中的作用。方法.在C57 BL/6野生型(WT)和TLR 9缺陷型(TLR 9-D)小鼠中通过升结肠支架腹膜炎(CASP)诱导脓毒症。在6、12、18、24和36 h测定腹膜腔中的细菌负荷和炎性介质的心脏表达。CASP后18小时,在体内监测心脏功能。分离的心肌细胞的肌节长度在与热灭活的细菌孵育后在0.5至10 Hz下测量。结果CASP导致细菌持续释放到腹膜腔中,细胞因子增加,以及心脏先天免疫受体的差异调节。CASP后18小时,WT小鼠出现脓毒性心力衰竭,其特征是收缩末期压、每搏输出量、心输出量和收缩力参数降低。这与心肌细胞肌节缩短减少相一致。TLR 9缺乏导致心脏炎症的显著减少和持续的心脏功能。这与与WT小鼠相比TLR 9-D的死亡率降低一致。结论.在多微生物败血症中,TLR 9信号传导对于心脏炎症和脓毒性心力衰竭是关键的。
Background. Aim was to elucidate the role of toll-like receptor 9 (TLR9) in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis. Methods. Sepsis was induced via colon ascendens stent peritonitis (CASP) in C57BL/6 wild-type (WT) and TLR9-deficient (TLR9-D) mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h. Eighteen hours after CASP cardiac function was monitored in vivo. Sarcomere length of isolated cardiomyocytes was measured at 0.5 to 10 Hz after incubation with heat-inactivated bacteria. Results. CASP led to continuous release of bacteria into the peritoneal cavity, an increase of cytokines, and differential regulation of receptors of innate immunity in the heart. Eighteen hours after CASP WT mice developed septic heart failure characterised by reduction of end-systolic pressure, stroke volume, cardiac output, and parameters of contractility. This coincided with reduced cardiomyocyte sarcomere shortening. TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function. This was consistent with reduced mortality in TLR9-D compared to WT mice. Conclusions. In polymicrobial sepsis TLR9 signalling is pivotal to cardiac inflammation and septic heart failure.
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发表时间: 2000-11-28
期刊: CIRCULATION
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影响因子: 4.6
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