Enhanced monocyte chemoattractant protein-1 production in aging mice exaggerates cardiac depression during endotoxemia.
Enhanced monocyte chemoattractant protein-1 production in aging mice exaggerates cardiac depression during endotoxemia.
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DOI：
10.1186/s13054-014-0527-8
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发表时间：
2014-09-11
期刊：
影响因子：
--
通讯作者：
Meng X
中科院分区：
文献类型：
--
作者：
Slimani H;Zhai Y;Yousif NG;Ao L;Zeng Q;Fullerton DA;Meng X
内毒素血症和全身炎症反应综合征对术后结果有显著影响，特别是在老年人中。细胞因子对内毒素的反应会因衰老而改变。我们检验了这样一个假设，即内毒素性心脏抑制的易感性随着年龄的增长而增加，这是由于与年龄相关的心肌炎症反应增加。用内毒素（0.5 mg/kg，iv）处理成年（4至6个月）和老年（20至22个月）C57/BL 6小鼠。使用微导管系统评估左心室（LV）功能。酶联免疫吸附试验（ELISA）检测血浆和心肌组织中的趋化因子和细胞因子。用免疫荧光染色法检测心肌单核细胞。内毒素处理后，老年小鼠显示出更差的LV功能（心输出量：3.0 ± 0.2 mL/min，成年小鼠为4.4 ± 0.3 mL/min）。老年小鼠心脏抑制加重与血浆和心肌中单核细胞趋化蛋白-1（MCP-1）和角质形成细胞趋化因子（KC）水平升高、心肌中单核细胞聚集增多以及血浆和心肌中肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1β）和白细胞介素-6（IL-6）水平升高有关。MCP-1的中和导致心肌单核细胞积聚和细胞因子产生的更大减少，以及老年小鼠LV功能的更大改善，而KC的中和对LV功能的影响最小。老年小鼠对内毒素血症的炎症反应增强，导致过度的心脏功能抑制。MCP-1促进心肌单个核细胞聚集和心肌细胞因子的产生，在老年小鼠内毒素性心肌病的发病中起重要作用。研究结果表明，需要特别注意保护老年人内毒素血症的心脏。
Endotoxemia and the systemic inflammatory response syndrome have a significant impact on post-surgery outcome, particularly in the elderly. The cytokine response to endotoxin is altered by aging. We tested the hypothesis that vulnerability to endotoxemic cardiac depression increases with aging due to age-related augmentation of myocardial inflammatory responses. Adult (4 to 6 months) and old (20 to 22 months) C57/BL6 mice were treated with endotoxin (0.5 mg/kg, iv). Left ventricle (LV) function was assessed using a microcatheter system. Chemokines and cytokines in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells in the myocardium were examined using immunofluorescence staining. Old mice displayed worse LV function (cardiac output: 3.0 ± 0.2 mL/min versus 4.4 ± 0.3 mL/min in adult mice) following endotoxin treatment. The exaggerated cardiac depression in old mice was associated with higher levels of monocyte chemoattractant protein-1 (MCP-1) and keratinocyte chemoattractant (KC) in plasma and myocardium, greater myocardial accumulation of mononuclear cells, and greater levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6) in plasma and myocardium. Neutralization of MCP-1 resulted in greater reductions in myocardial mononuclear cell accumulation and cytokine production, and greater improvement in LV function in old mice while neutralization of KC had a minimal effect on LV function. Old mice have enhanced inflammatory responses to endotoxemia that lead to exaggerated cardiac functional depression. MCP-1 promotes myocardial mononuclear cell accumulation and cardiodepressant cytokines production, and plays an important role in the endotoxemic cardiomyopathy in old mice. The findings suggest that special attention is needed to protect the heart in the elderly with endotoxemia.
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影响因子：
64.8
作者：
OHLSSON, K;BJORK, P;THOMPSON, RC
通讯作者：
THOMPSON, RC
影响因子：
3.1
作者：
Maass, DL;White, J;Horton, JW
通讯作者：
Horton, JW
影响因子：
15.9
作者：
OKUSAWA, S;GELFAND, JA;DINARELLO, CA
通讯作者：
DINARELLO, CA
DOI：
10.1152/ajpheart.1998.275.3.h1016
发表时间：
1998-09-01
影响因子：
4.8
作者：
Panas, D;Khadour, FH;Schulz, R
通讯作者：
Schulz, R
DOI：
10.1164/ajrccm.152.2.7633696
发表时间：
1995-08-01
影响因子：
24.7
作者：
HERBERTSON, MJ;WERNER, HA;WALLEY, KR
通讯作者：
WALLEY, KR