Purpose: This study aims to explore the potential mechanism of dexmedetomidine in terms of inhibiting inflammation to alleviate early neuronal injury via TLR4/NF- κB pathway in rats with traumatic brain injury. Methods: The model of brain injury was established in rats. After the model was established, the rats were randomly divided into five groups: Sham, Sham + DEX, TBI, TBI + vehicle, and TBI + DEX. Each group included 10 rats. The water content in the brain tissue was measured. Terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL) assays were performed on histopathological tissue sections to evaluate neuronal apoptosis. Enzyme-linked immunosorbent assay and PCR were applied to detect the levels of the inflammatory factors, TNF-a, IL1b, IL-6, and NF-kB. Results: TBI–challenged rats exhibited significant neuronal apoptosis, which was characterized via the wet-to-dry weight ratio, neurobehavioral functions, TUNEL assay results and the levels of cleaved caspase-3, Bax upregulation and Bcl-2, which were attenuated by DEX. Western blot, immunohistochemistry, and PCR results revealed that DEX promoted TLR4 expression and upregulated expression of the TLR4 downstream factors, HO-1 and NQO-1. Furthermore, DEX treatment markedly prevented the downregulation of inflammatory response factors, TNF-a, IL-1β and NF-kB, and IL-6. Conclusion: Dexmedetomidine is able to inhibit inflammation and attenuate early neuronal injury in rats with acute brain injury, which may act on TLR4/NF- κB pathway.

中文翻译：

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右美托咪定通过 TLR4/NF-?B 通路抑制炎症减轻大鼠脑外伤早期神经元损伤

目的：本研究旨在探讨右美托咪定通过TLR4/NF-κB通路抑制脑外伤大鼠炎症减轻早期神经元损伤的潜在机制。方法：建立大鼠脑损伤模型。模型建立后，将大鼠随机分为5组：Sham、Sham+DEX、TBI、TBI+载体、TBI+DEX。每组包括10只大鼠。测量脑组织中的水含量。在组织病理学组织切片上进行末端脱氧核苷酸转移酶介导的 dUTP 缺口标记 (TUNEL) 检测以评估神经元凋亡。应用酶联免疫吸附法和 PCR 检测炎症因子、TNF-a、IL1b、IL-6 和 NF-kB 的水平。结果：TBI 攻击的大鼠表现出显着的神经元凋亡，其特征在于湿干重量比、神经行为功能、TUNEL 测定结果以及裂解的 caspase-3、Bax 上调和 Bcl-2 的水平，这些水平被 DEX 减弱。蛋白质印迹、免疫组织化学和 PCR 结果显示 DEX 促进 TLR4 表达并上调 TLR4 下游因子 HO-1 和 NQO-1 的表达。此外，DEX 治疗显着阻止了炎症反应因子、TNF-a、IL-1β 和 NF-kB 以及 IL-6 的下调。结论：右美托咪定能抑制急性脑损伤大鼠的炎症反应，减轻早期神经元损伤，其可能作用于TLR4/NF-κB通路。被 DEX 削弱了。蛋白质印迹、免疫组织化学和 PCR 结果显示 DEX 促进 TLR4 表达并上调 TLR4 下游因子 HO-1 和 NQO-1 的表达。此外，DEX 治疗显着阻止了炎症反应因子、TNF-a、IL-1β 和 NF-kB 以及 IL-6 的下调。结论：右美托咪定能抑制急性脑损伤大鼠的炎症反应，减轻早期神经元损伤，其可能作用于TLR4/NF-κB通路。被 DEX 削弱了。蛋白质印迹、免疫组织化学和 PCR 结果显示 DEX 促进 TLR4 表达并上调 TLR4 下游因子 HO-1 和 NQO-1 的表达。此外，DEX 治疗显着阻止了炎症反应因子、TNF-a、IL-1β 和 NF-kB 以及 IL-6 的下调。结论：右美托咪定能抑制急性脑损伤大鼠的炎症反应，减轻早期神经元损伤，其可能作用于TLR4/NF-κB通路。