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Methoxytetrahydro‐2H‐pyran‐2‐yl)methyl benzoate inhibits spinal cord injury in the rat model via PPAR‐γ/PI3K/p‐Akt activation
Environmental Toxicology ( IF 4.4 ) Pub Date : 2020-03-09 , DOI: 10.1002/tox.22902
Hao Zhang 1 , Ming Gong 1 , Xinle Luo 1
Affiliation  

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.

中文翻译:

Methoxytetrahydro-2H-pyran-2-yl)methyl benzoate 通过 PPAR-γ/PI3K/p-Akt 激活抑制大鼠模型脊髓损伤

脊髓损伤 (SCI) 是世界范围内最常见的导致残疾的创伤。本研究的目的是确定甲氧基四氢-2H-吡喃-2-基苯甲酸甲酯 (HMPB) 对大鼠模型 SCI 的保护作用。TUNEL 染色用于检测 SCI 大鼠脊髓的凋亡变化。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。蛋白质印迹用于评估蛋白质。基于施用的剂量浓度,SCI大鼠的HMPB治疗减少了凋亡细胞数。用HMPB治疗SCI大鼠显着提高了BBB评分并显着降低了SCI大鼠的水分积累。用 HMPB 治疗后,SCI 大鼠的 TNF-α 和白细胞介素-6/1β/18 水平受到抑制。用 HMPB 处理诱导 SOD、CAT 和 GSH 分子的过度释放并减少 MDA 的过量产生。SCI 诱导的 caspase-3/9 活性上调被 HMPB 以 2 mg/kg 剂量完全缓解。SCI 大鼠的 HMPB 治疗促进了过氧化物酶体增殖物激活受体 γ (PPAR-γ) 的表达,减少了环氧合酶 (COX)-2 的产生并增加了 p-Akt 和磷酸肌醇 3-激酶 (p-PI3K) 的表达。该研究表明,HMPB 可抑制 SCI 大鼠的细胞凋亡、提高 BBB 评分并抑制炎症。此外,HMPB促进了SCI大鼠脊髓组织中PI3K/Akt的激活。因此,HMPB在大鼠模型中对SCI具有保护作用。
更新日期:2020-03-09
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