Department of Neurosurgery, Ninth Hospital of Xi'an, Xi'an 710000, China.
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
J Environ Pathol Toxicol Oncol. 2021;40(4):11-19. doi: 10.1615/JEnvironPatholToxicolOncol.2021038860.
Cerebral ischemic reperfusion (I/R) infarction is mostly associated with serious brain injury, cognitive damage, and neurological deficits. The oxidative stress mechanisms in the neurological region lead to higher reactive oxygen species production followed by oxidative stress, inflammation of neurons, and death of brain cells. The current work aims to evaluate the effect of troxerutin (TXN) on cerebral injury stimulated by I/R-induced ischemic stroke and examines the mechanistic effect of TXN on neuroinflammation in the Sprague Dawley model. The experimental rats were randomized in to four groups: (i) sham control, (ii) I/R + vehicle, (iii) I/R + 10 mg/kg bw TXN, and (iv) I/R + 20 mg/kg bw TXN. In the TXN administration and control, groups were injected intraperitoneally 15 min before reperfusion and every day for 7 days, except the sham group. Orally administered TXN (10 and 20 mg/kg/bw) modulated the water content, lowered the infarct volume, and abrogated score defects of neuron and changes in the brain tissue sample. In our study, the TXN-stimulated cerebral injury exhibited leakage of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) of the neuronal sample of tissues and showed higher antioxidant enzymes superoxide dismutase, catalase, the oxidized form of glutathione peroxidase, and the reduced form of glutathione levels. This biochemical result was additionally proved by histopathological assessment. Changes were made in antioxidant and inflammatory markers expressions interleukin-6 (IL-6), IL-4, IL-10, vascular endothelial growth factor, and cerebral induced rats. The overall findings showed that TXN protected the brain tissues from neuroinflammatory oxidative stress by reducing cerebral injury in Sprague Dawley rats. Further, the messenger RNA expression of cerebral I/R-induced animal tissues down-regulated NLRP3, caspase-1, tumor necrosis factor-α, ASC, IL-1β, and Toll-like receptor 3 (TLR3). Therefore, the TXN action on TLR3 induced brain stroke is an excellent therapeutic approach for brain damage.
脑缺血再灌注（I/R）梗死主要与严重脑损伤、认知损伤和神经功能缺损有关。神经区域的氧化应激机制导致活性氧（ROS）产生增加，随后发生氧化应激、神经元炎症和脑细胞死亡。本研究旨在评估曲克芦丁（TXN）对缺血性脑卒中诱导的 I/R 引起的脑损伤的影响，并研究 TXN 对 Sprague Dawley 模型中神经炎症的机制作用。实验大鼠随机分为四组：（i）假手术对照，（ii）I/R+载体，（iii）I/R+10mg/kg bw TXN，和（iv）I/R+20mg/kg bw TXN。在 TXN 给药和对照中，各组在再灌注前 15 分钟腹腔内注射，并在 7 天内每天注射，除假手术组外。口服给予 TXN（10 和 20mg/kg/bw）调节水含量，降低梗死体积，并减轻神经元评分缺陷和脑组织样本的变化。在我们的研究中，TXN 刺激的脑损伤表现出硫代巴比妥酸反应物质（TBARS）的渗漏、组织神经元样本的脂质过氧化物（LOOH），并显示出更高的抗氧化酶超氧化物歧化酶、过氧化氢酶、氧化型谷胱甘肽过氧化物酶和还原型谷胱甘肽水平。这一生化结果还通过组织病理学评估得到了证实。抗氧化和炎症标志物表达的变化发生在白细胞介素-6（IL-6）、白细胞介素-4（IL-4）、白细胞介素-10（IL-10）、血管内皮生长因子和诱导脑损伤的大鼠中。总体研究结果表明，TXN 通过减少 Sprague Dawley 大鼠的脑损伤来保护脑组织免受神经炎症氧化应激的影响。此外，脑 I/R 诱导的动物组织中的信使 RNA 表达下调了 NLRP3、半胱天冬酶-1、肿瘤坏死因子-α、ASC、IL-1β和 Toll 样受体 3（TLR3）。因此，TXN 对 TLR3 诱导的脑卒中有作用是一种治疗脑损伤的极好方法。
