胃饥饿素可保护大鼠皮质神经元免受局灶性缺血/再灌注损伤。

Ghrelin protects cortical neuron against focal ischemia/reperfusion in rats.

作者信息

Miao Yanying, Xia Qing, Hou Zhongchi, Zheng Yan, Pan Hui, Zhu Shigong

机构信息

Department of Physiology and Pathophysiology, Peking University Health Science Center, 38 Xueyuan Road, Haidian district, Beijing 100083, People's Republic of China.

出版信息

Biochem Biophys Res Commun. 2007 Aug 3;359(3):795-800. doi: 10.1016/j.bbrc.2007.05.192. Epub 2007 Jun 6.

DOI:10.1016/j.bbrc.2007.05.192

PMID:17560544

Abstract

Ghrelin is a novel brain-gut peptide and the endogenous ligand of growth hormone secretagogue receptor 1a (GHSR-1a). Evidences have been shown that ghrelin inhibited cell apoptosis in cardiocytes, endotheliocytes, osteoblasts, and so on. Recently, it was reported that ghrelin inhibited neuronal apoptosis of hypothalamus and hippocampus. However, little is known about the effects of ghrelin on cortical neurons during focal ischemia/reperfusion injury. In the present study, we showed that ghrelin (i.v.) prevented cortical neurons from injury induced by ischemia/reperfusion in vivo and by LPS, glutamate, NMDA and H(2)O(2) in vitro. We found that the expression of ghrelin's receptor (GHSR-1a) in rat cerebral cortex were obviously decreased by ischemia/reperfusion injury and increased by ghrelin (i.v.). Ghrelin up-regulated the expression of Bcl-2/Bax and HSP70, and inhibited caspase8, 9, 3 through GHSR-1a, which was contributed to the neuroprotective mechanism of ghrelin. Ghrelin might be an important regulator in therapeutic strategy of cortex injury.

摘要

胃饥饿素是一种新型脑肠肽，是生长激素促分泌素受体1a（GHSR-1a）的内源性配体。已有证据表明，胃饥饿素可抑制心肌细胞、内皮细胞、成骨细胞等的细胞凋亡。最近，有报道称胃饥饿素可抑制下丘脑和海马体的神经元凋亡。然而，关于胃饥饿素在局灶性缺血/再灌注损伤期间对皮质神经元的影响知之甚少。在本研究中，我们发现静脉注射胃饥饿素可在体内防止皮质神经元受到缺血/再灌注损伤，在体外防止其受到脂多糖、谷氨酸、N-甲基-D-天冬氨酸和过氧化氢的损伤。我们发现，缺血/再灌注损伤可使大鼠大脑皮质中胃饥饿素受体（GHSR-1a）的表达明显降低，而静脉注射胃饥饿素则可使其表达增加。胃饥饿素通过GHSR-1a上调Bcl-2/Bax和热休克蛋白70（HSP70）的表达，并抑制半胱天冬酶8、9、3，这有助于胃饥饿素的神经保护机制。胃饥饿素可能是皮质损伤治疗策略中的一种重要调节因子。