Targeting Interleukin-1 beta to Suppress Sympathoexcitation in Hypothalamic Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats
Targeting Interleukin-1 beta to Suppress Sympathoexcitation in Hypothalamic Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats
复制标题
靶向 IL-1 Betato 抑制 Dahl 盐敏感高血压大鼠下丘脑室旁核的交感神经兴奋
DOI：
10.1007/s12012-015-9338-7
复制
发表时间：
2016-07-01
影响因子：
3.2
通讯作者：
Kang, Yu-Ming
中科院分区：
文献类型：
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作者：
Qi, Jie;Zhao, Xiu-Fang;Kang, Yu-Ming
我们实验室的研究结果表明，下丘脑室旁核（PVN）中一些促炎细胞因子（例如肿瘤坏死因子、白细胞介素-6）和氧化应激反应的表达增加，并导致盐敏感性高血压的进展。在这项研究中，我们确定了 PVN 内白细胞介素 1 β (IL-1 β) 的激活是否有助于盐依赖性高血压发生过程中的交感神经兴奋。 8周龄雄性Dahl盐敏感(S)大鼠接受高盐饮食(HS，8% NaCl)或正常盐饮食(NS，0.3% NaCl)6周，所有大鼠每周一次双侧PVN注射gevokizumab(IL-1β抑制剂，1μL 10μg)或载体。高盐喂养大鼠的平均动脉压（MAP）、心率（HR）和血浆去甲肾上腺素（NE）显着增加。此外，与正常饮食的大鼠相比，高盐饮食的大鼠PVN中NOX-2、NOX-4（NAD（P）H氧化酶的亚基）、IL-1β、NLRP3（包含pyrin结构域的NOD样受体家族家族3）、Fra-LI（慢性神经元激活的指标）水平较高，而IL-10水平较低。双侧PVN注射gevokizumab可降低MAP、HR和NE，减轻氧化应激水平并恢复细胞因子的平衡。这些发现表明 PVN 中 IL-1 β 的激活在盐敏感性高血压中发挥作用。
Findings from our laboratory indicate that expressions of some proinflammatory cytokines such as tumor necrosis factor, interleukin-6 and oxidative stress responses are increased in the hypothalamic paraventricular nucleus (PVN) and contribute to the progression of salt-sensitive hypertension. In this study, we determined whether interleukin-1 beta (IL-1 beta) activation within the PVN contributes to sympathoexcitation during development of salt-dependent hypertension. Eight-week-old male Dahl salt-sensitive (S) rats received a high-salt diet (HS, 8 % NaCl) or a normal-salt diet (NS, 0.3 % NaCl) for 6 weeks, and all rats were treated with bilateral PVN injection of gevokizumab (IL-1 beta inhibitor, 1 mu L of 10 mu g) or vehicle once a week. The mean arterial pressure (MAP), heart rate (HR) and plasma norepinephrine (NE) were significantly increased in high-salt-fed rats. In addition, rats with high-salt diet had higher levels of NOX-2, NOX-4 [subunits of NAD (P) H oxidase], IL-1 beta, NLRP3 (NOD-like receptor family pyrin domain containing 3), Fra-LI (an indicator of chronic neuronal activation) and lower levels of IL-10 in the PVN than normal-diet rats. Bilateral PVN injection of gevokizumab decreased MAP, HR and NE, attenuated the levels of oxidative stress and restored the balance of cytokines. These findings suggest that IL-1 beta activation in the PVN plays a role in salt-sensitive hypertension.