Zhang Kun, Liu Yu, Liu Xiaoqiang, Chen Jie, Cai Qingqing, Wang Jingfeng, Huang Hui
Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou 510120, China.
Oncotarget. 2015 Sep 22;6(28):24699-708. doi: 10.18632/oncotarget.5084.
Cardiac remodeling is one of the most common cardiac abnormalities and associated with a high mortality in chronic renal failure (CRF) patients. Apocynin, a nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been showed cardio-protective effects. However, whether apocynin can improve cardiac remodeling in CRF and what is the underlying mechanism are unclear. In the present study, we enrolled 94 participants. In addition, we used 5/6 nephrectomized rats to mimic cardiac remodeling in CRF. Serum levels of epoxyeicosatrienoic acids (EETs) and its mainly metabolic enzyme-soluble epoxide hydrolase (sEH) were measured. The results showed that the serum levels of EETs were significantly decreased in renocardiac syndrome participants (P < 0.05). In 5/6 nephrectomized CRF model, the ratio of left ventricular weight / body weight, left ventricular posterior wall thickness, and cardiac interstitial fibrosis were significantly increased while ejection fraction significantly decreased (P < 0.05). All these effects could partly be reversed by apocynin. Meanwhile, we found during the process of cardiac remodeling in CRF, apocynin significantly increased the reduced serum levels of EETs and decreased the mRNA and protein expressions of sEH in the heart (P < 0.05). Our findings indicated that the protective effect of apocynin on cardiac remodeling in CRF was associated with the up-regulation of EETs. EETs may be a new mediator for the injury of kidney-heart interactions.
心脏重塑是最常见的心脏异常之一,与慢性肾衰竭(CRF)患者的高死亡率相关。Apocynin是一种烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶抑制剂,已显示出心脏保护作用。然而,Apocynin是否能改善CRF患者的心脏重塑及其潜在机制尚不清楚。在本研究中,我们招募了94名参与者。此外,我们使用5/6肾切除大鼠来模拟CRF中的心脏重塑。测量了血清环氧二十碳三烯酸(EETs)及其主要代谢酶可溶性环氧水解酶(sEH)的水平。结果显示,肾心综合征参与者的血清EETs水平显著降低(P<0.05)。在5/6肾切除的CRF模型中,左心室重量/体重比、左心室后壁厚度和心脏间质纤维化显著增加,而射血分数显著降低(P<0.05)。所有这些影响均可被Apocynin部分逆转。同时,我们发现在CRF心脏重塑过程中,Apocynin显著提高了降低的血清EETs水平,并降低了心脏中sEH的mRNA和蛋白表达(P<0.05)。我们的研究结果表明,Apocynin对CRF心脏重塑的保护作用与EETs的上调有关。EETs可能是肾心相互作用损伤的新介质。