Haydarpasa Numune Education and Research Hospital, Department of Neurosurgery, Istanbul, Turkey.
J Neurotrauma. 2010 Jun;27(6):1143-55. doi: 10.1089/neu.2009.1210.
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 microg/kg/d IP) SAH groups. The rats were injected with blood (0.3 mL) 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-100beta protein, TNF-alpha, and IL-1beta 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-100beta, TNF-alpha, and IL-1beta 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.
为了阐明 Ghrelin 在蛛网膜下腔出血（SAH）诱导的脑损伤中的潜在神经保护作用，将 Wistar 白化大鼠（n = 54）分为假手术对照、盐水处理的 SAH 和 Ghrelin 处理（10μg/kg/d IP）SAH 组。向大鼠枕大池内注射血液（0.3 mL）以诱导 SAH，并在记录神经检查评分后 48 小时处死。评估血浆样本中的神经元特异性烯醇化酶（NSE）、S-100β蛋白、TNF-α 和 IL-1β 水平，同时取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。获得包含基底动脉的脑组织样本进行组织学检查，同时取出大脑和小脑测量血脑屏障（BBB）通透性和脑水含量。SAH 诱导 48 小时后神经评分受损，SAH 导致大脑 GSH 含量和 Na(+)-K(+)-ATP 酶活性显著降低，化学发光、MDA 水平和 MPO 活性增加。与对照组相比，血浆中 NSE、S-100β、TNF-α 和 IL-1β 的蛋白水平也升高，而 Ghrelin 治疗可预防所有在生化和组织病理学上观察到的 SAH 诱导的改变。结果表明，Ghrelin 通过维持氧化应激状态的平衡、抑制促炎介质和防止 SAH 引起的内源性抗氧化剂耗竭，减轻 SAH 诱导的氧化脑损伤，并发挥神经保护作用。
