Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis.
Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis.
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DOI：
10.1186/cc12889
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发表时间：
2013-09-10
期刊：
影响因子：
--
通讯作者：
Wischmeyer PE
中科院分区：
文献类型：
--
作者：
Wilson J;Higgins D;Hutting H;Serkova N;Baird C;Khailova L;Queensland K;Vu Tran Z;Weitzel L;Wischmeyer PE
阻断β-肾上腺素能受体的药物与烧伤预后的改善有关。据推测，导致高代谢状态的损伤，如感染性休克，也可能受益于β-受体阻滞剂;然而，实验模型的结果数据是矛盾的。因此，我们研究了普萘洛尔β受体阻滞剂对大鼠盲肠结扎穿孔（CLP）脓毒症模型的存活率、血流动力学、肺热休克蛋白（HSP）表达、代谢和炎症标志物的影响。接受普萘洛尔或对照（生理盐水）重复给药（CLP前30分钟和术后24小时每8小时给药一次）的Sprague-Dawley大鼠进行CLP并监测存活率。此外，在6小时和24小时采集肺和血液样品用于分析。还对动物进行监测以评价总体血流动力学。CLP术后7天，普萘洛尔组与对照组相比，生存率提高（P < 0.01）。在最初24小时内，普萘洛尔治疗大鼠的心率比对照大鼠低约23%（P < 0.05），但各组之间的平均动脉血压没有差异。肺组织的代谢分析表明，肺ATP/ADP比值和NAD+含量增加，多不饱和脂肪酸/单不饱和脂肪酸（PUFA/MUFA）比值降低。炎性细胞因子肿瘤坏死因子α（TNF-α）的细胞因子分析表明，在CLP诱导的脓毒症后24小时，肺和血浆中TNF-α的表达均降低。最后，普萘洛尔导致肺血红素氧合酶-1表达显著增加，这是肺中一种关键的细胞保护性热休克蛋白（HSP）。其他肺HSP表达无变化。这些结果表明，普萘洛尔治疗可能通过改善代谢、抑制炎症反应和增强组织保护的组合来降低脓毒症期间的死亡率。
Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory response and enhancing tissue protection.
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影响因子：
38.9
作者：
Mori, Katsuya;Morisaki, Hiroshi;Takeda, Junzo
通讯作者：
Takeda, Junzo
DOI：
10.1097/ta.0b013e318031afd3
发表时间：
2007-03-01
影响因子：
--
作者：
Jeschke, Marc G.;Norbury, William B.;Herndon, David N.
通讯作者：
Herndon, David N.
影响因子：
2.4
作者：
MINIFEE, PK;BARROW, RE;HERNDON, DN
通讯作者：
HERNDON, DN
影响因子：
8.8
作者：
Suzuki, T;Morisaki, H;Takeda, J
通讯作者：
Takeda, J
影响因子：
8.8
作者：
Singleton, KD;Serkova, N;Wischmeyer, PE
通讯作者：
Wischmeyer, PE