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Mechanisms of leptin receptor isoforms expression in heart diseases

瘦素受体亚型在心脏病中的表达机制

基本信息

批准号：
16590658
负责人：
YOKOYAMA Tomoyuki
金额：
$ 1.98万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590658/
关键词：
leptin leptin receptor ischemia reperfusion hypertrophy pressure overload

项目摘要

(1)Ischemia/reperfusion in rat heart induces leptin and leptin receptor gene expression.We examined the expression of leptin (ob) and leptin receptor (ob-R) genes in the rat heart following ischemia/reperfusion. Ischemia/reperfusion 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 mRNAs and proteins significantly exceeded amounts in control hearts after 8 h of reperfusion, and they were present at ischemic wound sites locally. To determine the functional effects of leptin in ischemic heart, rats were treated with anti-leptin antibodies prior to ischemia/reperfusion. This treatment partially prevented elevation of the mRNA expression levels of inflammatory markers such as TNF-α and IL-1β in ischemic hearts.(2)Hypertensive stress directly up-regulates expression of leptin and the long form of the lept … More in receptor (ob-Rb) in rat cardiac myocytesPressure overload was produced by ligation of the abdominal aorta. Using expression of the real-time polymerase chain reaction (PCR), leptin and the long form of the leptin receptor (ob-Rb) gene were significantly increased at 2 and 4 weeks, but expression of the short form of the leptin receptor (ob-Ra) was unchanged after banding. When we examined protein expression of ob-Rb, ob-Rb protein was detected by immunohistochemistry in hypertrophied cardiomyocytes. Plasma leptin concentrations were not different between the control and banding groups. To clarify which hypertension-related stimuli induces ob and ob-Rb expression in the heart, we examined ob and ob-Rb mRNA expression in neonatal rat cardiac myocytes treated with angiotensin II (ANGII), endothelin-1 (ET-1), or cyclic mechanical stretch. ANGII and ET-1 increased only ob mRNA expression. However, mechanical stretch activated both ob and ob-Rb expression in a time-dependent manner, but ob-Ra was unaffected by any stress. Less

（1）大鼠心脏缺血再灌注诱导瘦素及其受体基因表达我们检测了缺血再灌注后大鼠心脏瘦素（leptin，ob）和瘦素受体（leptin receptor，ob-R）基因的表达。通过冠状动脉结扎诱导缺血/再灌注，并在开始再灌注后0.5至36 h从心脏获得mRNA。实时荧光定量RT-PCR和免疫组化检测ob和ob-R mRNA的表达。ob和ob-Ra的mRNA和蛋白质显着超过对照组心脏再灌注8小时后的量，它们存在于局部缺血伤口部位。为了确定瘦素在缺血心脏中的功能作用，在缺血/再灌注之前用抗瘦素抗体处理大鼠。这种治疗部分阻止了缺血心脏中炎症标志物如TNF-α和IL-1β的mRNA表达水平的升高。（2）高血压应激直接上调瘦素和长型瘦素的表达， ...更多信息用腹主动脉结扎法造成大鼠心肌细胞压力超负荷。使用表达的实时聚合酶链反应（PCR），瘦素和瘦素受体（ob-Rb）基因的长形式显着增加，在2周和4周，但表达的瘦素受体（ob-Ra）的短形式是不变的显带后。在检测ob-Rb蛋白表达时，采用免疫组织化学方法检测肥大心肌细胞中ob-Rb蛋白的表达。血浆瘦素浓度之间没有显着差异的控制和绑定组。为了阐明高血压相关的刺激诱导ob和ob-Rb在心脏中的表达，我们研究了ob和ob-Rb mRNA表达的新生大鼠心肌细胞血管紧张素II（ANGII），内皮素-1（ET-1），或周期性机械拉伸。ANGII和ET-1仅增加ob mRNA表达。然而，机械拉伸激活ob和ob-Rb的表达在一个时间依赖性的方式，但ob-Ra不受任何应力。少