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藏红花醛通过抗凋亡、抗炎和减轻水肿对大鼠脊髓创伤模型的神经保护作用。

Neuroprotective effects of safranal in a rat model of traumatic injury to the spinal cord by anti-apoptotic, anti-inflammatory and edema-attenuating.

作者信息

Zhang Chen, Ma Jun, Fan Lihong, Zou Yulong, Dang Xiaoqian, Wang Kunzheng, Song Jinhui

机构信息

The First Department of Orthopaedics, the Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China.

The First Department of Orthopaedics, the Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, PR China.

出版信息

Tissue Cell. 2015 Jun;47(3):291-300. doi: 10.1016/j.tice.2015.03.007. Epub 2015 Apr 8.

Abstract

Studies on the pathology of spinal cord injury (SCI) have focused on inflammation-associated neuronal apoptosis. The traditional Chinese medicine safranal has been studied extensively and found to have various beneficial health effects. However, study of its potential role in neuroprotection and the underlying mechanism of action in SCI models has been limited. We investigated the effect of safranal on neurologic functions and histopathologic changes after SCI and the mechanism underlying its neuroprotective effects. First, the most effective safranal dose for SCI was evaluated with the Basso, Beattie, and Bresnahan Locomotor Rating Scale and H&E staining: 100mg/kg was the most effective dose of safranal for SCI. Histopathologic changes were evaluated by performing Nissl staining, which indicated an increased number of neurons after safranal administration. In terms of the mechanism of action, anti-apoptotic effect, downregulation of inflammation, and edema-attenuating effects were detected. TUNEL staining and electron microscopy revealed that safranal treatment inhibited injury-induced apoptosis, and affected the expression of the apoptosis-related genes Bax and Bcl-2, which indicated an anti-apoptotic role after SCI. Safranal treatment suppressed immunoreactivity and expression of the inflammatory cytokines IL-1β, TNF-α, and p38 MAPK, and increased expression of IL-10 after SCI, suggesting an anti-inflammatory effect. Safranal treatment suppressed expression of AQP-4, which is related to spinal-cord edema, suggesting an edema-attenuating effect. These data suggest that safranal promotes the recovery of neuronal function after SCI in rats, and that this effect is related to its anti-apoptotic, anti-inflammatory, and edema-attenuating effects.

摘要

脊髓损伤(SCI)的病理学研究主要集中在炎症相关的神经元凋亡方面。传统中药藏红花醛已得到广泛研究,并发现具有多种有益健康的作用。然而,关于其在脊髓损伤模型中的神经保护潜在作用及其潜在作用机制的研究却很有限。我们研究了藏红花醛对脊髓损伤后神经功能和组织病理学变化的影响及其神经保护作用的潜在机制。首先,采用Basso、Beattie和Bresnahan运动评分量表以及苏木精-伊红(H&E)染色评估藏红花醛对脊髓损伤最有效的剂量:100mg/kg是藏红花醛对脊髓损伤最有效的剂量。通过尼氏染色评估组织病理学变化,结果表明给予藏红花醛后神经元数量增加。在作用机制方面,检测到其具有抗凋亡作用、炎症下调作用和减轻水肿的作用。TUNEL染色和电子显微镜检查显示,藏红花醛治疗可抑制损伤诱导的凋亡,并影响凋亡相关基因Bax和Bcl-2的表达,这表明在脊髓损伤后具有抗凋亡作用。藏红花醛治疗可抑制炎症细胞因子IL-1β、TNF-α和p38丝裂原活化蛋白激酶(p38 MAPK)的免疫反应性和表达,并增加脊髓损伤后IL-10的表达,提示具有抗炎作用。藏红花醛治疗可抑制与脊髓水肿相关的水通道蛋白4(AQP-4)的表达,提示具有减轻水肿的作用。这些数据表明,藏红花醛可促进大鼠脊髓损伤后神经元功能的恢复,且这种作用与其抗凋亡、抗炎和减轻水肿的作用有关。

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