Ischemia/reperfusion in rat heart induces leptin and leptin receptor gene expression
Ischemia/reperfusion in rat heart induces leptin and leptin receptor gene expression
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DOI：
10.1016/j.lfs.2006.10.027
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发表时间：
2007-01-23
期刊：
影响因子：
6.1
通讯作者：
Yokoyama, Tomoyuki
中科院分区：
文献类型：
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作者：
Matsui, Hiroki;Motooka, Masahiko;Yokoyama, Tomoyuki
瘦素是一种脂肪细胞产生的激素，其浓度在肥胖症中升高。近年来，研究表明瘦素参与多种生物学作用，包括炎症、生殖和血管生成。瘦素也被证明是伤口愈合过程中的关键成分;然而，瘦素与心血管疾病的关系却知之甚少。我们研究了瘦素（ob）和瘦素受体（ob-R）基因在大鼠心脏缺血/再灌注后的表达，这是由冠状动脉结扎引起的，并从心脏开始再灌注后0.5至36小时获得mRNA。实时荧光定量RT-PCR和免疫组化检测ob和ob-R mRNA的表达。再灌注8h，心肌ob和ob-Ra mRNA和蛋白表达明显增加（p < 0.01），ob-Rb mRNA表达明显减少（p < 0.01）。此外，ob和ob-R蛋白在损伤的心肌细胞中表达，炎性细胞浸润。相比之下，这些表达没有受到影响，在8小时的缺血应激后的心脏。为了确定瘦素对缺血/再灌注心脏的功能影响，在缺血/再灌注之前用抗瘦素抗体治疗大鼠;然而，这种治疗并不影响缺血心脏中炎症标志物如TNF-α和IL-1 β的mRNA表达水平的升高。我们的研究结果首次表明，缺血/再灌注诱导瘦素和瘦素受体基因表达的大鼠心脏。这项研究有助于阐明缺血性心脏病伴随肥胖的发病和发展背后的机制。(c)2006年爱思唯尔公司All rights reserved.
Concentrations of leptin, an adipocyte-derived hormone, are elevated in obesity. Recently, leptin has been shown to participate in multiple biological actions including inflammation, reproduction, and angiogenesis. Leptin has also been documented as a critical component in the process of wound healing; however, leptin involvement in cardiovascular disease is poorly understood. We examined the expression of leptin (ob) and leptin receptor (ob-R) genes in the rat heart following ischemia/reperfusion, which was induced by coronary artery ligation, and mRNA was obtained from hearts 0.5 to 36 h after initiating reperfusion. Expressions of ob and ob-R mRNA were examined by real-time quantitative RT-PCR and immunohistochemistry. The ob and ob-Ra mRNA and protein expressions were significantly increased (p < 0.01) and ob-Rb mRNA was significantly decreased (p < 0.01) in hearts after 8 h of reperfusion. Furthermore, ob and ob-R proteins were expressed in injured myocytes where inflammatory cells infiltrated. In contrast, those expressions were not influenced in hearts after 8 h of ischemia stress only. To determine the functional effects of leptin on the ischemic/reperfused heart, rats were treated with anti-leptin antibodies prior to ischemia/reperfusion; however, this treatment did not affect the elevation of mRNA expression levels of inflammatory markers such as TNF-alpha and IL-1 beta in ischemic hearts. Our results demonstrated for the first time that ischemia/reperfusion induced leptin and leptin receptor gene expression in the rat heart. This study helps to elucidate the mechanisms behind the onset and development of ischemic heart disease concomitant with obesity. (c) 2006 Elsevier Inc. All rights reserved.