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左旋肉碱和阿托伐他汀对大鼠脊髓缺血再灌注损伤模型的影响。

Effect of L-carnitine and atorvastatin on a rat model of ischemia-reperfusion injury of spinal cord.

机构信息

Medical Physiology, Menoufia University, Shebein Elkom, Egypt.

Pathology Departments, Faculty of Medicine, Menoufia University, Shebein Elkom, Egypt.

出版信息

J Immunoassay Immunochem. 2021 Nov 2;42(6):596-619. doi: 10.1080/15321819.2021.1914085. Epub 2021 Apr 26.

DOI:10.1080/15321819.2021.1914085
PMID:33900902
Abstract

Pro-inflammatory cytokines and reactive oxygen species (ROS) are produced in acute spinal cord injury, leading to myelin breakdown, inflammation, mitochondrial dysfunction, and apoptosis of neurons and glial cells. The aim of the present study was to investigate possible protective effects of L-carnitine (carn) or atorvastatin (ator) on spinal cord ischemia-reperfusion injury (IRI). Rats were randomized into nine equal groups (n = 8): control and control taking carn (100 mg/kg BW), ator (2.5 mg/kg BW) or both, as well as sham-operation, IRI and IRI taking same doses of carn, ator or both. Neurological assessments were done 48 hours after IRI, and serum nitrite/nitrate was measured. Finally, lumbar segments of spinal cord were excised, and part was homogenized and prepared for measuring tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), advanced oxidation protein products (AOPP), reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase. The other part was sectioned for evaluation of histopathological changes and for immunostaining by glial fibrillary acidic protein (GFAP), Bax and Bcl-2. The IRI increased ROS (nitrite/nitrate, MDA, AOPP) and pro-inflammatory cytokines (TNF-α, IL-1β), and decreased antioxidants (GSH, GPx, SOD, catalase) with impaired sensory and motor functions. Astrogliosis was detected by GFAP, and increased apoptosis was demonstrated by increasing Bax and decreasing Bcl-2. Treatment with carn or ator alone decreased TNF-α, IL-1β, nitrite/nitrate, MDA and AOPP, and increased GSH, GPx, SOD, and catalase with improvement of neurological functions and histological studies. Combination of carn and ator improved most of measured IRI-affected parameters better than isolated carn or ator administration.

摘要

促炎细胞因子和活性氧 (ROS) 在急性脊髓损伤中产生,导致髓鞘破裂、炎症、线粒体功能障碍以及神经元和神经胶质细胞凋亡。本研究旨在探讨左旋肉碱 (carn) 或阿托伐他汀 (ator) 对脊髓缺血再灌注损伤 (IRI) 的可能保护作用。大鼠随机分为 9 组 (n=8):对照组和给予 carn (100 mg/kg BW)、ator (2.5 mg/kg BW) 或两者的对照组,以及假手术组、IRI 组和给予相同剂量 carn、ator 或两者的 IRI 组。在 IRI 后 48 小时进行神经学评估,并测量血清亚硝酸盐/硝酸盐。最后,切除腰椎段脊髓,部分匀浆,准备测量肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)、丙二醛 (MDA)、高级氧化蛋白产物 (AOPP)、还原型谷胱甘肽 (GSH)、谷胱甘肽过氧化物酶 (GPx)、超氧化物歧化酶 (SOD) 和过氧化氢酶。另一部分用于评估组织病理学变化,并通过胶质纤维酸性蛋白 (GFAP)、Bax 和 Bcl-2 进行免疫染色。IRI 增加了 ROS (亚硝酸盐/硝酸盐、MDA、AOPP) 和促炎细胞因子 (TNF-α、IL-1β),并降低了抗氧化剂 (GSH、GPx、SOD、过氧化氢酶),同时感觉和运动功能受损。星形胶质细胞增生通过 GFAP 检测到,Bax 增加和 Bcl-2 减少表明细胞凋亡增加。单独给予 carn 或 ator 可降低 TNF-α、IL-1β、亚硝酸盐/硝酸盐、MDA 和 AOPP,增加 GSH、GPx、SOD 和过氧化氢酶,改善神经功能和组织学研究。与单独给予 carn 或 ator 相比,carn 和 ator 的联合使用改善了大多数受 IRI 影响的参数。

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