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首页> 外文期刊>American Journal of Physiology >TNF-alpha blockade decreases oxidative stress in the paraventricular nucleus and attenuates sympathoexcitation in heart failure rats.
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TNF-alpha blockade decreases oxidative stress in the paraventricular nucleus and attenuates sympathoexcitation in heart failure rats.

机译：TNF-α阻滞剂可降低心力衰竭大鼠心室旁核的氧化应激并减弱交感神经兴奋。

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摘要

Oxidative stress plays an important role in the pathophysiology of cardiovascular disease. Recent evidence suggests that cytokines induce oxidative stress and contribute to cardiac dysfunction. In this study, we investigated whether increased circulating and tissue levels of tumor necrosis factor (TNF)-alpha in congestive heart failure (CHF) modulate the expression of NAD(P)H oxidase subunits, Nox2 and its isoforms, in the paraventricular nucleus (PVN) of the hypothalamus and contribute to exaggerated sympathetic drive in CHF. Heart failure was induced in Sprague-Dawly rats by coronary artery ligation and was confirmed using echocardiography. Pentoxifylline (PTX) was used to block the production of cytokines for a period of 5 wk. CHF induced a significant increase in the production of reactive oxygen species (ROS) in the left ventricle (LV) and in the PVN. The mRNA and protein expression of TNF-alpha, Nox1, Nox2, and Nox4 was significantly increased in the LV and PVN of CHF rats. CHF also decreased ejection fraction, increased Tei index, and increased circulating catecholamines (epinephrine and norepinephrine) and renal sympathetic activity (RSNA). In contrast, treatment with PTX in CHF rats completely blocked oxidative stress and decreased the production of TNF-alpha and Nox2 isoforms both in the LV and PVN. PTX treatment also decreased catecholamines and RSNA and prevented further decrease in cardiac function. In summary, TNF-alpha blockade attenuates ROS and sympathoexcitation in CHF. This study unveils new mechanisms by which cytokines play a role in the pathogenesis of CHF, thus underscoring the importance of targeting cytokines in heart failure.
机译：氧化应激在心血管疾病的病理生理中起着重要作用。最近的证据表明，细胞因子诱导氧化应激并导致心脏功能障碍。在这项研究中，我们调查了充血性心力衰竭（CHF）中肿瘤坏死因子（TNF）-α的循环水平和组织水平是否增加，调节脑室旁核中NAD（P）H氧化酶亚基Nox2及其同工型的表达（下丘脑的PVN）并导致CHF的过度交感神经驱动。通过冠状动脉结扎在Sprague-Dawly大鼠中诱发心力衰竭，并通过超声心动图确认。己酮可可碱（PTX）在5周内用于阻止细胞因子的产生。 CHF导致左心室（LV）和PVN中活性氧（ROS）的产生显着增加。在CHF大鼠的LV和PVN中，TNF-α，Nox1，Nox2和Nox4的mRNA和蛋白表达显着增加。 CHF还可以降低射血分数，增加Tei指数，增加循环儿茶酚胺（肾上腺素和去甲肾上腺素）和肾交感神经活性（RSNA）。相反，在CHF大鼠中用PTX进行治疗可完全阻断氧化应激，并降低LV和PVN中TNF-α和Nox2亚型的产生。 PTX治疗还降低了儿茶酚胺和RSNA，并防止了心脏功能的进一步下降。总之，TNF-α阻断剂可减轻CHF中的ROS和交感神经兴奋。这项研究揭示了细胞因子在CHF发病机理中起作用的新机制，从而强调了在心力衰竭中靶向细胞因子的重要性。

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