Brain-Derived Neurotrophic Factor Attenuates Septic Myocardial Dysfunction via eNOS/NO Pathway in Rats.
Brain-Derived Neurotrophic Factor Attenuates Septic Myocardial Dysfunction via eNOS/NO Pathway in Rats.
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脑源性神经营养因子通过 eNOS/NO 途径减轻大鼠脓毒性心肌功能障碍
DOI：
10.1155/2017/1721434
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发表时间：
2017
影响因子：
--
通讯作者：
Xiao F
中科院分区：
文献类型：
--
作者：
Zeng N;Xu J;Yao W;Li S;Ruan W;Xiao F
脓毒症引起的心肌功能障碍增加脓毒症的死亡率，但其潜在机制尚不清楚。已发现脑源性神经营养因子（BDNF）可增强心肌细胞功能，但BDNF是否对脓毒性心肌功能障碍具有有益作用尚不清楚。采用盲肠结扎穿孔法（CLP）诱导感染性休克。BDNF在原代心肌细胞中表达，脓毒症后表达明显减少。在脓毒症大鼠中，CLP后观察到存活率急剧下降，心脏BDNF表达显著降低，心肌纤维化增强，氧化应激升高，心肌细胞凋亡增加，内皮型一氧化氮（NO）合酶（eNOS）和NO减少。补充重组BDNF蛋白（rhBDNF）可增强心肌BDNF，提高存活率，改善心功能，降低氧化应激，和心肌细胞凋亡，这与eNOS表达增加，NO产生，和Trk-B，BDNF受体。用NOS抑制剂N（omega）-nitro-L-arginine methyl ester预处理，可消除上述BDNF心脏保护作用，而不影响BDNF和Trk-B。结论BDNF通过Trk-B减少氧化应激和细胞凋亡，并通过激活eNOS/NO通路来保护心脏免受脓毒性心功能障碍。这些发现为脓毒症引起的心肌功能障碍提供了一种新的治疗策略。
Sepsis-induced myocardial dysfunction increases mortality in sepsis, yet the underlying mechanism is unclear. Brain-derived neurotrophic factor (BDNF) has been found to enhance cardiomyocyte function, but whether BDNF has a beneficial effect against septic myocardial dysfunction is unknown. Septic shock was induced by cecal ligation and puncture (CLP). BDNF was expressed in primary cardiomyocytes, and its expression was significantly reduced after sepsis. In rats with sepsis, a sharp decline in survival was observed after CLP, with significantly reduced cardiac BDNF expression, enhanced myocardial fibrosis, elevated oxidative stress, increased myocardial apoptosis, and decreased endothelial nitric oxide (NO) synthase (eNOS) and NO. Supplementation with recombined BDNF protein (rhBDNF) enhanced myocardial BDNF and increased survival rate with improved cardiac function, reduced oxidative stress, and myocardial apoptosis, which were associated with increased eNOS expression, NO production, and Trk-B, a BDNF receptor. Pretreatment with NOS inhibitor, N (omega)-nitro-L-arginine methyl ester, abolished the abovementioned BDNF cardioprotective effects without affecting BDNF and Trk-B. It is concluded that BDNF protects the heart against septic cardiac dysfunction by reducing oxidative stress and apoptosis via Trk-B, and it does so through activation of eNOS/NO pathway. These findings provide a new treatment strategy for sepsis-induced myocardial dysfunction.
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7.1
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