Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou City, China.
Cecile Cox Quillen Laboratory of Geriatrics, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA.
Neurochem Res. 2017 Oct;42(10):2949-2957. doi: 10.1007/s11064-017-2326-5. Epub 2017 Jun 12.
Previous studies have demonstrated that plasma resistin levels were increased in patients with acute ischemic stroke. However, the role of resistin after ischemic brain injury is still unclear. In this study, we investigated the protective effects of resistin on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that resistin (i.c.v.) significantly reduced infarct volume and improved neurological deficits after 45 min of ischemia and 24 h of reperfusion. Furthermore, our data demonstrate that intraperitoneal administration of resistin (10 µg/kg body weight) also had protective effects on infarct volume, indicating the crossing of resistin through the impaired BBB after ischemia injury. Resistin treatment reduced cleaved protein level of Poly(ADP-ribose)polymerase-1 (PARP-1), a marker of cellular apoptosis, showing the anti-apoptotic activity of resistin. Resistin increased the level of phosphorylated Akt after ischemic brain injury. The neuroprotective effect of resistin was partially reversed by a PI3K inhibitor wortmannin, demonstrating that the PI3K/Akt signal pathway is involved in the anti-apoptotic mechanisms of resistin. Finally, we found that resistin treatment improved neurological function recovery at 14 days after treatment, including balance ability and muscle strength. Given these findings, resistin may have therapeutic potential for the treatment of stroke.
先前的研究表明，急性缺血性脑卒中患者的血浆抵抗素水平升高。然而，抵抗素在缺血性脑损伤后的作用仍不清楚。在这项研究中，我们在大脑中动脉闭塞的小鼠模型中研究了抵抗素对脑缺血/再灌注损伤的保护作用。我们发现，抵抗素（脑室内注射）可显著减少 45 分钟缺血和 24 小时再灌注后的梗死体积并改善神经功能缺损。此外，我们的数据表明，腹腔内给予抵抗素（10μg/kg 体重）对梗死体积也有保护作用，表明抵抗素在缺血损伤后可通过受损的血脑屏障穿过。抵抗素治疗可降低细胞凋亡标志物聚（ADP-核糖）聚合酶-1（PARP-1）的裂解蛋白水平，表明抵抗素具有抗细胞凋亡作用。缺血性脑损伤后，抵抗素增加磷酸化 Akt 的水平。PI3K 抑制剂wortmannin 部分逆转了抵抗素的神经保护作用，表明 PI3K/Akt 信号通路参与了抵抗素的抗细胞凋亡机制。最后，我们发现抵抗素治疗可改善治疗后 14 天的神经功能恢复，包括平衡能力和肌肉力量。鉴于这些发现，抵抗素可能具有治疗中风的潜力。
