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肌肽减轻大鼠脑出血后的脑氧化应激和细胞凋亡

Carnosine Attenuates Brain Oxidative Stress and Apoptosis After Intracerebral Hemorrhage in Rats.

作者信息

Xie Rong-Xia, Li Da-Wei, Liu Xi-Chang, Yang Ming-Feng, Fang Jie, Sun Bao-Liang, Zhang Zong-Yong, Yang Xiao-Yi

机构信息

Key Lab of Cerebral Microcirculation at the Universities of Shandong, Life Science Research Centre of Taishan Medical University, Taian, 271016, Shandong, China.

出版信息

Neurochem Res. 2017 Feb;42(2):541-551. doi: 10.1007/s11064-016-2104-9. Epub 2016 Nov 21.

Abstract

Carnosine, an endogenous dipeptide (β-alanyl-L-histidine), exerts multiple neuroprotective properties, but its role in intracerebral hemorrhage (ICH) remains unclear. This study investigates the effect of Carnosine on brain injury using the rat ICH model, which is established by type IV collagenase caudatum infusion. The results indicate that intraperitoneal administration of Carnosine (1000 mg/kg) significantly attenuates brain edema, blood-brain barrier (BBB) disruption, oxidative stress, microglia activation and neuronal apoptosis of perihematoma at 72 h following ICH in rats models, as convinced by preventing the disruption of tight junction protein ZO-1, occludin and claudin-5, followed by the decrease of ROS, MDA, 3-NT, 8-OHDG level and the increase of GSH-Px and SOD activity, then followed by the decline of Iba-1, ED-1, active caspase-3 and TUNEL positive cells and the decrease of IL-1β, IL-6, TNF-α, active caspase-3 and cytochrome c level. Our results suggest that Carnosine may provide neuroprotective effect after experimental ICH in rat models.

摘要

肌肽是一种内源性二肽(β-丙氨酰-L-组氨酸),具有多种神经保护特性,但其在脑出血(ICH)中的作用仍不清楚。本研究使用通过向尾状核注入IV型胶原酶建立的大鼠ICH模型,研究肌肽对脑损伤的影响。结果表明,在大鼠ICH模型中,于ICH后72小时腹腔注射肌肽(1000mg/kg)可显著减轻脑水肿、血脑屏障(BBB)破坏、氧化应激、小胶质细胞活化和血肿周围神经元凋亡,这可通过防止紧密连接蛋白ZO-1、闭合蛋白和Claudin-5的破坏来证实,随后ROS、MDA、3-NT、8-OHDG水平降低,GSH-Px和SOD活性增加,进而Iba-1、ED-1、活化的caspase-3和TUNEL阳性细胞减少,IL-1β、IL-6、TNF-α、活化的caspase-3和细胞色素c水平降低。我们的结果表明,肌肽可能在大鼠实验性ICH后提供神经保护作用。

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