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甲氧基四氢-2H-吡喃-2-基)甲酯通过 PPAR-γ/PI3K/p-Akt 激活抑制大鼠脊髓损伤。

Methoxytetrahydro-2H-pyran-2-yl)methyl benzoate inhibits spinal cord injury in the rat model via PPAR-γ/PI3K/p-Akt activation.

机构信息

Department of Spinal surgery, The People's Hospital of Longhua, Shenzhen, China.

出版信息

Environ Toxicol. 2020 Jun;35(6):714-721. doi: 10.1002/tox.22902. Epub 2020 Mar 9.

Abstract

Spinal cord injury (SCI) is the most commonly seen trauma leading to disability in people worldwide. The purpose of current study was to determine the protective effect of methoxytetrahydro-2H-pyran-2-yl)methyl benzoate (HMPB) on SCI in rat model. TUNEL staining was used to examine apoptotic changes in spinal cord of SCI rats. The ELISA kits were employed to assess inflammatory processes and oxidative factors in the spinal cord tissues. Behavioral changes in SCI rats were assessed using Basso, Beattie, and Bresnahan (BBB) scoring system. Western blotting was used for assessment of proteins. The HMPB treatment of SCI rats reduced apoptotic cell number based on the concentration of dose administered. Treatment of SCI rats with HMPB enhanced BBB score and decreased accumulation of water content in SCI rats significantly. On treatment with HMPB the TNF-α and interleukin-6/1β/18 levels were suppressed in SCI rats. Treatment with HMPB induced excessive release of SOD, CAT, and GSH molecules and decreased overproduction of MDA. The SCI induced upregulation of caspase-3/9 activity was completely alleviated by HMPB at 2 mg/kg dose. The HMPB treatment of SCI rats promoted peroxisome proliferator-activated receptor γ (PPAR-γ) expression, reduced cyclooxygenase (COX)-2 production and increased expression of p-Akt and phosphoinositide 3-kinase (p-PI3K). The study demonstrated that HMPB suppressed apoptosis, raised BBB score and inhibited inflammation in SCI rats. Moreover, activation of PI3K/Akt in the spinal cord tissues of SCI rats was promoted by HMPB. Therefore, HMPB has protective effect on SCI in the rat model.

摘要

脊髓损伤 (SCI) 是全球范围内导致残疾最常见的创伤。本研究旨在确定甲氧基四氢-2H-吡喃-2-基)甲基苯甲酸酯 (HMPB) 对大鼠 SCI 模型的保护作用。TUNEL 染色用于检测 SCI 大鼠脊髓中的凋亡变化。ELISA 试剂盒用于评估脊髓组织中的炎症过程和氧化因子。使用 Basso、Beattie 和 Bresnahan (BBB) 评分系统评估 SCI 大鼠的行为变化。Western blot 用于评估蛋白质。根据给药浓度,HMPB 治疗 SCI 大鼠减少了凋亡细胞数量。HMPB 治疗 SCI 大鼠显著增强了 BBB 评分并减少了 SCI 大鼠的水分含量积累。HMPB 治疗降低了 SCI 大鼠 TNF-α 和白细胞介素-6/1β/18 水平。HMPB 诱导 SOD、CAT 和 GSH 分子过度释放,并减少 MDA 的过度产生。HMPB 在 2 mg/kg 剂量下完全缓解了 SCI 诱导的 caspase-3/9 活性的上调。HMPB 治疗 SCI 大鼠促进过氧化物酶体增殖物激活受体 γ (PPAR-γ) 表达,减少环氧化酶 (COX)-2 产生并增加 p-Akt 和磷酸肌醇 3-激酶 (p-PI3K) 的表达。该研究表明,HMPB 抑制了 SCI 大鼠的凋亡,提高了 BBB 评分并抑制了炎症。此外,HMPB 还促进了 SCI 大鼠脊髓组织中 PI3K/Akt 的激活。因此,HMPB 对大鼠 SCI 模型具有保护作用。

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