Physcion Protects Rats Against Cerebral Ischemia-Reperfusion Injury via Inhibition of TLR4/NF-kB Signaling Pathway.
Physcion Protects Rats Against Cerebral Ischemia-Reperfusion Injury via Inhibition of TLR4/NF-kB Signaling Pathway.
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DOI：
10.2147/dddt.s267856
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Wang G
中科院分区：
文献类型：
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作者：
Dong X;Wang L;Song G;Cai X;Wang W;Chen J;Wang G
缺血性卒中(IS)的特点是脑功能因缺血而迅速丧失。已发现大黄素甲素对脑缺血再灌注损伤有神经保护作用。然而，大黄素甲素调节脑I/R损伤的机制仍不清楚。分别建立SH-SY5Y细胞缺氧缺糖/再灌注(OGD/R)模型和大鼠脑缺血再灌注(I/R)模型。用CCK-8和流式细胞仪检测SH-SY5Y细胞的存活率和凋亡率。采用酶联免疫吸附试验检测SH-SY5Y细胞培养上清液中超氧化物歧化酶、丙二醛、谷胱甘肽过氧化物酶、肿瘤坏死因子α、白介素1β、白介素6和白介素10水平。用Western印迹法检测SH-SY5Y细胞和I/R大鼠肺组织中TLR4、p-P65和p-IκB的表达。在本研究中，大黄素甲素治疗显著挽救了OGD/R所致的神经元损伤。此外，大黄素甲素降低缺氧/再灌流后SH-SY5Y细胞的炎症反应，表现为促炎因子肿瘤坏死因子-α、IL-1β、IL-6和IL-10水平的降低。此外，大黄素甲素减轻了OGD/R处理的SY-SY5Y细胞的氧化应激，表现为增加了SOD和GSH水平，降低了ROS和MDA水平。同时，大黄素甲素可明显减轻I/R大鼠脑梗塞，减轻神经元损伤和细胞凋亡。此外，大黄素甲素可显著降低缺血再灌注大鼠脑组织和缺氧缺血再灌注后SH-SY5Y细胞中TLR4、p-NF-κB p65和p-IκB的表达。
Ischemic stroke (IS) is characterized by the rapid loss of brain function due to ischemia. Physcion has been found to have a neuroprotective effect against cerebral ischemia-reperfusion (I/R) injury. However, the mechanism by which physcion regulates cerebral I/R injury remains largely unknown. An oxygen-glucose deprivation/reperfusion (OGD/R) model in SH-SY5Y cells and a rat cerebral ischemia-reperfusion (I/R) model were established, respectively. CCK-8 and flow cytometry assays were used to detect the viability and apoptosis of SH-SY5Y cells. Moreover, enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of SOD, MDA, GSH-Px, TNF-α, IL-1β, IL-6 and IL-10 in the supernatant of SH-SY5Y cells. Meanwhile, Western blot assay was used to detect the expressions of TLR4, p-p65 and p-IκB in SH-SY5Y cells and I/R rats. In this study, physcion treatment significantly rescued OGD/R-induced neuronal injury. In addition, physcion decreased inflammatory response in SH-SY5Y cells after OGD/R insult, as shown by the decreased levels of the pro-inflammatory factors TNF-α, IL-1β, IL-6 and IL-10. Moreover, physcion attenuated the oxidative stress in OGD/R-treated SY-SY5Y cells, as evidenced by the increased SOD and GSH levels and the decreased ROS and MDA levels. Meanwhile, physcion significantly reduced cerebral infarction, attenuated neuronal injury and apoptosis in I/R rats. Furthermore, physcion markedly decreased the expressions of TLR4, p-NF-κB p65 and p-IκB in the brain tissues of rats subjected to I/R and in SH-SY5Y cells exposed to OGD/R. In conclusion, our study indicated that physcion protected neuron cells against I/R injury in vitro and in vivo by inhibition of the TLR4/NF-kB pathway; thus, physcion might serve as a promising therapeutic candidate for IS.