Leptin Reduces Infarct Size in Association with Enhanced Expression of CB2, TRPV1, SIRT-1 and Leptin Receptor
Leptin Reduces Infarct Size in Association with Enhanced Expression of CB2, TRPV1, SIRT-1 and Leptin Receptor
复制标题
DOI：
10.2174/156720210791184943
复制
发表时间：
2010-05-01
影响因子：
2.1
通讯作者：
Leker, Ronen R.
中科院分区：
文献类型：
--
作者：
Avraham, Yosefa;Davidi, Neta;Leker, Ronen R.
脑缺血与能量产生和利用的有害变化有关。因此，我们假设瘦素，一种脂肪细胞分裂素激素，可以防止严重的能量消耗，减少梗死体积并改善卒中后的功能结局。雄性Sabra小鼠通过光血栓形成进行永久性大脑中动脉闭塞（PMCAO）。在初始剂量反应和时间窗实验后，用载体或瘦素处理动物，每天通过神经系统严重程度评分（NSS）进行检查，并在中风后72小时处死。测定脑体积，并定量皮质中参与神经保护和存活的关键基因的表达，包括大麻素受体CB（1）、CB（2）和TRPV 1、SIRT-1、瘦素受体和Bcl-2。在中风后1、24和48小时以及1、2和3周用神经学严重程度量表检查单独的一组小鼠，并在中风后3周处死以检查梗塞周围区域的代谢状态。PMCAO后30分钟腹腔注射1 mg/kg瘦素可明显改善神经功能障碍，缩小梗死体积。瘦素处理导致CB（2）受体、TRPV 1、SIRT-1和瘦素受体表达增加，CB（1）受体表达减少。也有一个非显着增加Bcl-2基因表达瘦素管理。这些结果表明，瘦素可用于减轻缺血性损伤后中风通过诱导抗凋亡状态。
Brain ischemia is associated with detrimental changes in energy production and utilization. Therefore, we hypothesized that leptin, an adipokynin hormone protecting against severe energy depletion, would reduce infarct volume and improve functional outcome after stroke. Male Sabra mice underwent permanent middle cerebral artery occlusion (PMCAO) by photothrombosis. Following initial dose-response and time-window experiments animals were treated with vehicle or leptin, were examined daily by a neurological severity score (NSS) and were sacrificed 72 hours after stroke. Infarct volume was determined and the expression of key genes involved in neuroprotection and survival including the cannabinoid receptors CB(1), CB(2) and TRPV1, SIRT-1, leptin receptor and Bcl-2 was quantified in the cortex. A separate group of mice were examined with the neurological severity scale 1, 24 and 48 hours and 1, 2 and 3 weeks after stroke, and were killed 3 weeks post stroke to examine metabolic status in the peri-infarct area. Leptin given at a dose of 1mg/kg intra-peritoneally 30 minutes after PMCAO significantly improved neurological disability and reduced infarct volume. Leptin treatment led to increased expression of CB(2) receptor, TRPV1, SIRT-1 and leptin receptor and reduced expression of CB(1) receptor. There was also a non-significant increase in Bcl-2 gene expression following leptin administration. These results suggest that leptin may be used for attenuating ischemic injury after stroke via induction of an anti-apoptotic state.