Increased resistance to LPS-induced myocardial dysfunction in the Brown Norway rats versus Dahl S rats: roles of inflammatory cytokines and nuclear factor kappaB pathway.
Increased resistance to LPS-induced myocardial dysfunction in the Brown Norway rats versus Dahl S rats: roles of inflammatory cytokines and nuclear factor kappaB pathway.
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DOI：
10.1097/shk.0b013e3181b7819e
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Shi Y
中科院分区：
文献类型：
--
作者：
Du J;An J;Wei N;Guan T;Pritchard KA Jr;Shi Y
我们以前证明，布朗挪威（BN）大鼠的心脏比Dahl S（SS）大鼠的心脏更耐缺血性损伤。在这里，我们确定了这些大鼠对LPS诱导的心肌病的易感性，并检查了炎症信号的参与。两种菌株均用LPS（20 mg/kg）通过腹膜内注射处理6 h。Langendorff系统评价心肌功能，酶联免疫吸附试验测定促炎细胞因子。LPS显著降低两种品系的左心室发展压力。有趣的是，BN大鼠心脏的左室发展压力的下降比SS大鼠心脏低约25%。此外，LPS显著降低SS心脏的收缩峰值速率和舒张峰值速率，但在BN心脏中没有。在BN和SS大鼠之间没有观察到LPS诱导的冠状动脉流速降低的差异。此外，BN大鼠血浆和心脏中LPS诱导的促炎细胞因子TNF-α、IL-1β和IL-6的增加均显著低于SS大鼠。LPS显著上调SS心脏中促炎酶iNOS和环氧合酶2的表达，但在BN心脏中不上调。有趣的是，LPS并不刺激Toll样受体4或其适配体髓样分化因子88在两种品系心脏中的表达，但确实增加了IκB和P65磷酸化，在BN心脏中不如在SS心脏中显著。这些数据表明，促炎细胞因子的产生减少和核因子κB活化减少是BN心脏比SS心脏更能抵抗LPS诱导的心肌功能障碍的主要机制。
We previously demonstrated that hearts from Brown Norway (BN) rats were more resistant to ischemic injury than hearts from Dahl S (SS) rats. Here we determined the susceptibility to LPS-induced cardiomyopathy in these rats and examined the involvement of inflammatory signaling. Both strains were treated with LPS (20 mg/kg) via i.p. injection for 6 h. Myocardial function was assessed by the Langendorff system, and proinflammatory cytokines were measured by the enzyme-linked immunosorbent assay. LPS significantly reduced left ventricular developed pressure in both strains. Interestingly, the decrease of left ventricular developed pressure in BN rat hearts was approximately 25% less than that in SS rat hearts. Furthermore, LPS significantly reduced the peak rate of contraction and the peak rate of relaxation in SS hearts but not in BN hearts. No differences in LPS-induced decreases in coronary flow rate were observed between BN and SS rats. In addition, LPS-induced increases in proinflammatory cytokines, TNF-α, IL-1β, and IL-6, were significantly lower in both plasma and hearts of BN rats compared with production in SS rats. LPS notably up-regulated the expression of proinflammatory enzymes, iNOS and cyclooxygenase 2, in SS hearts but not in BN hearts. Interestingly, LPS did not stimulate Toll-like receptor 4 or its adaptor myeloid differentiation factor 88 expression in the hearts of either strain but did increase IκB and P65 phosphorylation, less prominently in BN hearts than in SS hearts. These data indicate that reduced production of proinflammatory cytokines and diminished nuclear factor κB activation are major mechanisms by which BN hearts are more resistant to LPS-induced myocardial dysfunction than SS hearts.