The Anti-Inflammatory and Neuroprotective Effects of Ghrelin in Subarachnoid Hemorrhage-Induced Oxidative Brain Damage in Rats
The Anti-Inflammatory and Neuroprotective Effects of Ghrelin in Subarachnoid Hemorrhage-Induced Oxidative Brain Damage in Rats
复制标题
DOI：
10.1089/neu.2009.1210
复制
发表时间：
2010-06-01
影响因子：
4.2
通讯作者：
Yegen, Berrak C.
中科院分区：
文献类型：
--
作者：
Ersahin, Mehmet;Toklu, Hale Z.;Yegen, Berrak C.
为了阐明生长素释放肽在蛛网膜下腔出血（SAH）诱导的脑损伤中的假定神经保护作用，将Wistar白化病大鼠（n=54）分为假手术对照组、盐水处理的SAH组和生长素释放肽处理（10 μ g/kg/d IP）的SAH组。大鼠枕大池内注射血液（0.3mL）诱导SAH，48 h后处死，记录神经功能评分。在血浆样本中，评价神经元特异性烯醇化酶（NSE）、S-100 β蛋白、TNF-α和IL-1 β水平，同时采集前脑组织样本，测量丙二醛（MDA）、谷胱甘肽（GSH）、活性氧水平、髓过氧化物酶（MPO）、Na+-K+-ATP酶活性和DNA片段化率。取含基底动脉的脑组织进行组织学检查，同时取出大脑和小脑进行血脑屏障（BBB）通透性和脑含水量的测量。SAH后48 h神经功能评分明显下降，脑组织GSH含量和Na+-K+-ATP酶活性显著降低，化学发光、MDA含量和MPO活性显著升高。与对照组相比，血浆中NSE，S-100 β，TNF-α和IL-1 β的蛋白水平也增加，而ghrelin治疗阻止了所有SAH诱导的生化和组织病理学变化。结果表明，生长激素释放肽减轻SAH诱导的氧化性脑损伤，并发挥神经保护作用，通过维持氧化-抗氧化状态的平衡，抑制促炎介质，并防止SAH诱发的内源性抗氧化剂的消耗。
To elucidate the putative neuroprotective effects of ghrelin in subarachnoid hemorrhage (SAH)- induced brain injury, Wistar albino rats (n=54) were divided into sham-operated control, saline-treated SAH, and ghrelin-treated (10 mu g/kg/d IP) SAH groups. The rats were injected with blood (0.3mL) into the cisterna magna to induce SAH, and were sacrificed 48 h after the neurological examination scores were recorded. In plasma samples, neuron-specific enolase (NSE), S-100 beta protein, TNF-alpha, and IL-1 beta levels were evaluated, while forebrain tissue samples were taken for the measurement of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species levels, myeloperoxidase (MPO), Na+-K+-ATPase activity, and DNA fragmentation ratio. Brain tissue samples containing the basilar arteries were obtained for histological examination, while cerebrum and cerebellum were removed for the measurement of blood-brain barrier (BBB) permeability and brain water content. The neurological scores were impaired at 48 h after SAH induction, and SAH caused significant decreases in brain GSH content and Na+-K+-ATPase activity, and increases in chemiluminescence, MDA levels, and MPO activity. Compared with the control group, the protein levels of NSE, S-100 beta, TNF-alpha, and IL-1 beta in plasma were also increased, while ghrelin treatment prevented all SAH-induced alterations observed both biochemically and histopathologically. The results demonstrate that ghrelin alleviates SAH-induced oxidative brain damage, and exerts neuroprotection by maintaining a balance in oxidant-antioxidant status, by inhibiting proinflammatory mediators, and preventing the depletion of endogenous antioxidants evoked by SAH.