Lysozyme: a mediator of myocardial depression and adrenergic dysfunction in septic shock in dogs
Lysozyme: a mediator of myocardial depression and adrenergic dysfunction in septic shock in dogs
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DOI：
10.1016/s0022-2828(03)00004-x
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发表时间：
2003-03-01
影响因子：
5
通讯作者：
Light, RB
中科院分区：
文献类型：
--
作者：
Mink, SN;Jacobs, H;Light, RB
本研究的目的是确定的性质，可过滤的心血管活性物质（FCS），有助于在犬模型的大肠杆菌感染性休克心肌功能障碍。在先前的研究中，发现菌血症4小时后血浆中FCS增加（Am J Physiol 1993;264：H1402），其中FCS通过包括右心室小梁（RVT）制备的生物测定法鉴定。在该研究中，FCS仅通过孔过滤技术部分鉴定，并且发现是分子量在10和30 K之间的蛋白质。在本研究中，FCS进一步纯化的尺寸排阻高压液相色谱法，直到一个单一的带被确定在一维凝胶电泳。然后对该条带进行串联质谱和蛋白质测序技术，两种技术均将FCS鉴定为溶菌酶c（Lzm-S），与源自犬脾脏的一致。验证性测试表明，在体内制剂中脓毒症期间达到的浓度下，纯化的Lzm-S在RVT制剂中产生心肌抑制。此外，Lzm-S在体外制剂中抑制由场刺激和β-激动剂异丙肾上腺素诱导的肾上腺素能反应，这些结果表明Lzm-S可抑制脓毒症中的交感神经反应。目前的研究结果表明，Lzm-S起源于从器官，如脾脏的白细胞崩解，有助于在这个模型中的心肌功能障碍。其机制可能与其结合或水解心肌膜糖蛋白，从而干扰心肌兴奋-收缩偶联在脓毒症。(C)2003爱思唯尔科技有限公司版权所有。
The objective of the present study was to identify the nature of a filterable cardiodepressant substance (FCS) that contributes to myocardial dysfunction in a canine model of Escherichia coli septic shock. In a previous study, it was found that FCS increased in plasma after 4 h of bacteremia (Am J Physiol 1993;264:H1402) in which FCS was identified by a bioassay that included a right ventricular trabecular (RVT) preparation. In that study, FCS was only partially identified by pore filtration techniques and was found to be a protein of molecular weight between 10 and 30 K. In the present study, FCS was further purified by size exclusion high-pressure liquid chromatography, until a single band was identified on one-dimensional gel electrophoresis. This band was then subjected to tandem mass spectrometry and protein-sequencing techniques and both techniques identified FCS as lysozyme c (Lzm-S), consistent with that originating from the canine spleen. Confirmatory tests showed that purified Lzm-S produced myocardial depression in the RVT preparation at concentrations achieved during sepsis in the in vivo preparation. In addition, Lzm-S inhibited the adrenergic response induced by field stimulation and the beta- agonist isoproterenol in in vitro preparations, these results suggesting that Lzm-S may inhibit the sympathetic response in sepsis. The present findings indicate that Lzm-S originating from disintegrating leukocytes from organs such as the spleen contributes to myocardial dysfunction in this model. The mechanism may relate to its binding or hydrolysis of a cardiac membrane glycoprotein thereby interfering with myocardial excitation-contraction coupling in sepsis. (C) 2003 Elsevier Science Ltd. All rights reserved.