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洛伐他汀对大鼠创伤性脊髓损伤的神经保护作用。

Neuroprotective effects of lovastatin against traumatic spinal cord injury in rats.

机构信息

Neuroscience Research Center, Aja University of Medical Sciences, Tehran, Iran.

Amol Faculty of Paramedicine, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

J Chem Neuroanat. 2022 Nov;125:102148. doi: 10.1016/j.jchemneu.2022.102148. Epub 2022 Aug 27.

Abstract

BACKGROUND

Lovastatin, as a drug of statins subgroup, has been conceptualized to have anti-inflammatory, antioxidant, and anti-apoptotic properties. Accordingly, the present study aimed to investigate the neuroprotective ramification of lovastatin on spinal cord injury (SCI).

MATERIAL AND METHODS

Seventy-five female adult Wistar rats were divided into five groups (n = 15). In addition to non-treated (Control group) and laminectomy alone (Sham group), SCI animals were randomly assigned to non-treated spinal cord injury (SCI group), treated with 2 mg/kg of lovastatin (Lova 2 group), and treated with 5 mg/kg of lovastatin (Lova 5 group). At the end of the study, to evaluate the treatments, MDA, CAT, SOD, and GSH factors were evaluated biochemically, apoptosis and gliosis were assessed by immunohistochemical while measuring caspase-3 and GFAP antibodies, and inflammation was estimated by examining the expression of IL-10, TNF-α, and IL-1β genes. The stereological method was used to appraise the total volume of the spinal cord at the site of injury, the volume of the central cavity created, and the density of neurons and glial cells in the traumatic area. In addition, Basso-Beattie-Bresnehan (BBB) and narrow beam test (NBT) were utilized to rate neurological functions.

RESULTS

Our results exposed the fact that biochemical factors (except MDA), stereological parameters, and neurological functions were significantly ameliorated in both lovastatin-treated groups, especially in Lova 5 ones, compared to the SCI group. The expression of the IL-10 gene was significantly upregulated in both lovastatin-treated groups compared to the SCI group and was considerably heighten in Lova 5 group. Expression of TNF-α and IL-1β, as well as the rate of apoptosis and GFAP positive cells significantly decreased in both lovastatin treated groups compared to the SCI group, and it was more pronounced in the Lova 5 ones.

CONCLUSION

Overall, using lovastatin, especially at a dose of 5 mg/kg, has a dramatic neuroprotective impact on SCI treatment.

摘要

背景

洛伐他汀作为他汀类药物亚组的一种药物,被认为具有抗炎、抗氧化和抗细胞凋亡的特性。因此,本研究旨在探讨洛伐他汀对脊髓损伤(SCI)的神经保护作用。

材料和方法

75 只雌性成年 Wistar 大鼠分为 5 组(n=15)。除未治疗(对照组)和单纯椎板切除术(假手术组)外,SCI 动物还随机分为未治疗脊髓损伤(SCI 组)、给予 2mg/kg 洛伐他汀(Lova 2 组)和给予 5mg/kg 洛伐他汀(Lova 5 组)。在研究结束时,为了评估治疗效果,通过免疫组织化学评估 MDA、CAT、SOD 和 GSH 因子,通过评估 caspase-3 和 GFAP 抗体评估细胞凋亡和神经胶质增生,并通过检查 IL-10、TNF-α 和 IL-1β 基因的表达来估计炎症。立体学方法用于评估损伤部位脊髓的总体积、中央腔形成的体积以及创伤区域神经元和神经胶质细胞的密度。此外,使用 Basso-Beattie-Bresnehan(BBB)和窄光束测试(NBT)评估神经功能。

结果

我们的结果表明,与 SCI 组相比,两种洛伐他汀治疗组的生化因子(MDA 除外)、立体学参数和神经功能均显著改善,尤其是 Lova 5 组。与 SCI 组相比,两种洛伐他汀治疗组的 IL-10 基因表达均显著上调,且 Lova 5 组明显升高。与 SCI 组相比,两种洛伐他汀治疗组的 TNF-α 和 IL-1β 表达以及细胞凋亡和 GFAP 阳性细胞的比例均显著降低,且 Lova 5 组更为明显。

结论

总的来说,使用洛伐他汀,尤其是 5mg/kg 的剂量,对 SCI 治疗具有显著的神经保护作用。

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