Mechanisms of leptin receptor isoforms expression in heart diseases

(1)大鼠心脏缺血再灌注诱导瘦素及瘦素受体基因表达。冠脉结扎法复制大鼠心肌缺血再灌注模型，再灌流后0.5~36h心脏组织中均有mRNA的表达。用实时荧光定量RT-PCR和免疫组织化学方法检测ob和ob-RmRNA的表达。再灌流8h后，心肌组织中ob和ob-Ra的mRNAs和蛋白含量均显著高于对照组，且局部存在于缺血创面。为确定瘦素在缺血心脏中的功能作用，在大鼠缺血/再灌注前给予抗瘦素抗体治疗。这种治疗部分阻止了缺血心脏炎症标志物如肿瘤坏死因子-α和IL-1β的表达水平的升高。(2)高血压应激直接上调瘦素和LEPT…的长形表达结扎腹主动脉可引起大鼠心肌细胞压力超负荷。实时定量聚合酶链式反应(PCR)检测结果显示，术后2周和4周，瘦素和长型瘦素受体(ob-Rb)基因表达显著增加，而短型瘦素受体(ob-Ra)基因表达无明显变化。在检测ob-Rb蛋白表达时，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。血浆瘦素浓度在对照组和环扎组之间无差异。为了阐明哪些高血压相关刺激诱导心脏ob和ob-Rb的表达，我们检测了血管紧张素II(AngII)、内皮素-1(ET-1)或周期性机械拉伸处理的新生大鼠心肌细胞ob和ob-Rb的mRNA表达。AngII和ET-1仅增加ob基因的表达。然而，机械拉伸以时间依赖的方式激活ob和ob-Rb的表达，但ob-Ra不受任何应力的影响。较少

(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