Protocatechuic acid exerts protective effects via suppression of the P38/JNK- NF-κB signalling pathway in an experimental mouse model of intracerebral haemorrhage.
Protocatechuic acid exerts protective effects via suppression of the P38/JNK- NF-κB signalling pathway in an experimental mouse model of intracerebral haemorrhage.
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原儿茶酸通过抑制 P38/JNK-NF-kappa B 信号通路在脑出血实验小鼠模型中发挥保护作用
DOI：
10.1016/j.ejphar.2019.03.008
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发表时间：
2019-07
期刊：
影响因子：
--
通讯作者：
Bian Liuguan
中科院分区：
文献类型：
--
作者：
Xi Zhiyu;Hu Xibei;Chen Xiao;Yang Yong;Ren Jie;Wang Baofeng;Zhong Zhihong;Sun Yuhao;Yang Guo-Yuan;Sun Qingfang;Bian Liuguan
原儿茶酸（PCA）在多种疾病中的神经保护作用已被广泛研究，但其在脑出血（ICH）中的作用尚未见报道。本研究验证了PCA对ICH的保护作用，并探讨了其相关机制。注射胶原酶建立脑出血模型。小鼠在手术后立即开始接受PCA治疗，每天一次，持续3天。分别于术后第1、3、7天进行改良神经功能缺损评分（mNSS）。第3天处死部分小鼠，比较脑组织含水量、促炎细胞因子表达及血肿周围组织细胞凋亡的变化。此外，SH-SY 5 Y细胞用氯化血红素处理以模拟ICH的继发性损伤。将细胞与PCA孵育以进行处理。检测细胞活力、活性氧、凋亡率、凋亡相关蛋白、丝裂原活化蛋白激酶（MAPKs）和核因子-κB（NF-κB）的蛋白表达。结果显示，PCA能明显减轻脑出血后3天的脑水肿，并能明显改善神经功能。PCA还降低了体内TNF-α、IL-1β和IL-6的蛋白和基因表达。PCA剂量依赖性地减少ROS的产生和细胞凋亡率。PCA剂量依赖性地降低bax表达，裂解caspase-3，增加bcl-2表达，下调P38/JNK-NF-κB通路。结论：PCA通过抑制氧化应激、炎症反应和细胞凋亡，有效改善脑出血小鼠的预后。其机制可能与下调P38/JNK-NF-κB通路有关，PCA可能是一种潜在的脑出血治疗药物。
Protocatechuic acid (PCA) has been well studied for its neuroprotection value in several diseases, but the effect in intracerebral haemorrhage (ICH) has not been reported. Here we verified the protection of PCA in ICH, and investigated the relative mechanisms. ICH model mice were established by injection of collagenase IV. The mice were treated with PCA once per day for 3 days, starting immediately after operation. The modified neurological severity score (mNSS) of mice at 1st, 3rd and 7th day after operation were recorded. And some of mice were euthanized at 3rd day to compare brain water content, pro-inflammatory cytokines expression, and cell apoptosis in perihematomal tissue. Additionally, SH-SY5Y cells were treated hemin to mimic secondary injury of ICH. Cells were incubated with PCA for treatment. The cell viability, ROS, apoptosis rate and protein expression of apoptosis-relative protein and MAPKs and NF-κB were detected and analysed. The results revealed PCA alleviated the cerebral oedema at 3rd post ICH, and significantly improved neurological functions. PCA also attenuated the protein and gene expression of TNF-а, IL-1β and IL-6 vivo. PCA dose-dependently decreased the generation of ROS and apoptosis rate. Furthermore, PCA treatment dose-dependently decreased the expression of bax, cleaved caspase-3, increased bcl-2 expression; PCA downregulated P38/JNK-NF-κB pathway. In conclusion, PCA effectively improves prognosis of ICH mice by inhibiting oxidative stress, inflammation and apoptosis. The mechanism possibly results of downregulating of P38/JNK-NF-κB pathway, and PCA can be a potential therapeutic agent for ICH.
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影响因子：
8.3
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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影响因子：
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作者：
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