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Physcion Protects Rats Against Cerebral Ischemia-Reperfusion Injury via Inhibition of TLR4/NF-kB Signaling Pathway
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2021-01-25 , DOI: 10.2147/dddt.s267856
Xiaobo Dong 1 , Lei Wang 1 , Guangrong Song 1 , Xu Cai 1 , Wenxin Wang 1 , Jiaqi Chen 1 , Gesheng Wang 1
Affiliation  

Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.



中文翻译:

Physcion 通过抑制 TLR4/NF-kB 信号通路保护大鼠免受脑缺血再灌注损伤

背景:缺血性中风 (IS) 的特征是由于缺血导致脑功能迅速丧失。已发现 Physcion 对脑缺血再灌注 (I/R) 损伤具有神经保护作用。然而,physcion 调节脑 I/R 损伤的机制仍然很大程度上未知。
方法:分别建立SH-SY5Y细胞氧葡萄糖剥夺/再灌注(OGD/R)模型和大鼠脑缺血再灌注(I/R)模型。CCK-8 和流式细胞术检测用于检测 SH-SY5Y 细胞的活力和凋亡。此外,采用酶联免疫吸附试验(ELISA)检测SH-SY5Y细胞上清液中SOD、MDA、GSH-Px、TNF-α、IL-1β、IL-6和IL-10的含量。同时采用Western blot法检测SH-SY5Y细胞和I/R大鼠TLR4、p-p65和p-IκB的表达。
结果:在这项研究中,物理治疗显着挽救了 OGD/R 诱导的神经元损伤。此外,physcion 降低了 OGD/R 损伤后 SH-SY5Y 细胞的炎症反应,如促炎因子 TNF-α、IL-1β、IL-6 和 IL-10 水平的降低所示。此外,physcion 减弱了 OGD/R 处理的 SY-SY5Y 细胞中的氧化应激,这可以通过 SOD 和 GSH 水平增加以及 ROS 和 MDA 水平降低来证明。同时,physcion 显着减少 I/R 大鼠的脑梗塞、减轻神经元损伤和细胞凋亡。此外,physcion 显着降低了 I/R 大鼠脑组织和 OGD/R 暴露 SH-SY5Y 细胞中 TLR4、p-NF-κB p65 和 p-IκB 的表达。
结论:总之,我们的研究表明,physcion 通过抑制 TLR4/NF-kB 通路在体外和体内保护神经元细胞免受 I/R 损伤。因此,physcion 可能成为治疗 IS 的有希望的候选药物。

更新日期:2021-01-25
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