Glycine-Histidine-Lysine (GHK) Alleviates Neuronal Apoptosis Due to Intracerebral Hemorrhage via the miR-339-5p/VEGFA Pathway.
Glycine-Histidine-Lysine (GHK) Alleviates Neuronal Apoptosis Due to Intracerebral Hemorrhage via the miR-339-5p/VEGFA Pathway.
复制标题
甘氨酸-组氨酸-赖氨酸 (GHK) 通过 miR-339-5p/VEGFA 途径减轻脑出血引起的神经元凋亡
DOI：
10.3389/fnins.2018.00644
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发表时间：
2018
影响因子：
4.3
通讯作者：
He Z
中科院分区：
文献类型：
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作者：
Zhang H;Wang Y;He Z
甘氨酸-组氨酸-赖氨酸（GHK）是一种人体三肽，可促进伤口愈合，对神经退行性疾病发挥神经保护作用，并促进组织再生。本研究探讨了GHK是否能减轻脑出血（ICH）损伤。简单地说，GHK预处理组成年Wistar大鼠每24 h注射一次GHK(1或10 mg/kg， i.p)，连续3天。在脑出血后第3天检测大鼠的含水量和完整神经元，并在脑出血后第4、24、72、168 h检测大鼠的神经功能缺损评分。凋亡通过caspase-3免疫组化、Nissl染色和TUNEL法检测。我们还通过Western blotting检测了GHK对SH-SY5Y细胞相关蛋白表达的影响。通过实时聚合酶链反应分析检测miR-339-5p的表达。GHK改善脑出血大鼠神经功能缺损，降低脑含水量，抑制神经元凋亡。hemin对SH-SY5Y细胞的凋亡也有抑制作用。此外，GHK下调miR-339-5p的表达，miR-339-5p的过表达部分逆转了SH-SY5Y细胞中GHK的抗凋亡作用。我们的研究结果表明，p38 MAPK通路参与了ghk诱导的miR-339-5p的下调，miR-339-5p/VEGFA轴在ICH损伤后的神经元凋亡预防中发挥作用。这些发现表明，GHK可能是脑出血的一种新的治疗策略。
Glycine-histidine-lysine (GHK) is a human tripeptide that enhances wound healing, exerts neuroprotective effects against neurodegenerative disease, and improves tissue regeneration. This study examined whether GHK can alleviate injury due to intracerebral hemorrhage (ICH). Briefly, adult Wistar rats in GHK pretreatment groups were injected with GHK (1 or 10 mg/kg, i.p.) every 24 h for 3 days. Water content and intact neurons were detected in the rats 3 days after ICH, and the neurological deficit scores were examined in the rats at 4, 24, 72, and 168 h after ICH. Apoptosis was evaluated via caspase-3 immunohistochemistry, Nissl staining, and TUNEL assay. We also examined the effect of GHK on the expression of related proteins in SH-SY5Y cells via Western blotting. The expression of miR-339-5p was examined via real-time polymerase chain reaction analyses. GHK improved neurological deficits, reduced water content in the brain and inhibited neuronal apoptosis in ICH rats. It also prevented the apoptosis of SH-SY5Y cells with hemin treatment. Furthermore, GHK downregulated miR-339-5p expression, and overexpression of miR-339-5p partially reversed the anti-apoptotic effects of GHK in SH-SY5Y cells. Our findings suggest that the p38 MAPK pathway is involved in the GHK-induced downregulation of miR-339-5p, and that the miR-339-5p/VEGFA axis plays a role in preventing neuronal apoptosis following ICH injury. These findings indicate that GHK may represent a novel therapeutic strategy for ICH.
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影响因子：
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作者：
Park JR;Lee H;Kim SI;Yang SR
通讯作者：
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影响因子：
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作者：
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通讯作者：
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