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积雪草苷通过抗氧化、抗炎作用以及抑制p38丝裂原活化蛋白激酶(p38-MAPK)机制减轻脊髓损伤的影响。

Asiaticoside attenuates the effects of spinal cord injury through antioxidant and anti‑inflammatory effects, and inhibition of the p38‑MAPK mechanism.

作者信息

Luo Yang, Fu Changfeng, Wang Zhenyu, Zhang Zhuo, Wang Hongxia, Liu Yi

机构信息

Department of Spinal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.

Department of Orthopaedics, General Hospital of Chinese PLA, Beijing 100853, P.R. China.

出版信息

Mol Med Rep. 2015 Dec;12(6):8294-300. doi: 10.3892/mmr.2015.4425. Epub 2015 Oct 9.

Abstract

Asiaticoside has potent pharmacological activity and broader pharmacological effects, including anti‑oxidant, antidepressant and hepatic protection effects, and the inhibition of tumor cell proliferation. However, the mechanism underlying the effects of asiaticoside on neurological pain in spinal cord injury (SCI) remain to be fully elucidated. Therefore, the present study investigated the specific mechanism underlying the beneficial action of asiaticoside in a SCI rat model. In the present study, Basso, Beattie and Bresnahan scores was determined to analyze the therapeutic effects of asiaticoside on the neurological function of the SCI rat model. The water content of the spinal cord was also determined to measure its effects on the SCI rats. Oxidative stress, levels of nitric oxide and inflammation were detected using commercial kits. Western blot analysis was used to measure the protein expression levels of p38‑mitogen‑activated protein kinase (MAPK) in the SCI rat. Asiaticoside effectively augmented the Basso, Beattie and Bresnahan scores of the SCI rats. Significant reductions in the water content of the spinal cord, the levels of inducible nitric oxide synthase (iNOS), and the activities of the nuclear factor‑κB p65 unit, tumor necrosis factor‑α, interleukin(IL)‑1β and IL‑6 were observed in the experimental animals. Furthermore, on examination of the oxidative stress‑associated parameters, increased production of malondialdehyde and decreased levels of superoxide dismutase, glutathione and glutathione peroxidase were detected in the SCI rat model. Asiaticoside also significantly suppressed the expression of p38‑MAPK, which indicated that the therapeutic effects of asiaticoside may be associated with the p38‑MAPK pathway. These data confirmed that asiaticoside attenuates SCI through antioxidant and anti‑inflammatory effects, and through inhibition of the p38‑MAPK mechanism.

摘要

积雪草苷具有强大的药理活性和广泛的药理作用,包括抗氧化、抗抑郁和肝脏保护作用,以及抑制肿瘤细胞增殖。然而,积雪草苷对脊髓损伤(SCI)所致神经病理性疼痛的作用机制仍有待充分阐明。因此,本研究探讨了积雪草苷在SCI大鼠模型中发挥有益作用的具体机制。在本研究中,测定了Basso、Beattie和Bresnahan评分,以分析积雪草苷对SCI大鼠模型神经功能的治疗效果。还测定了脊髓的含水量,以衡量其对SCI大鼠的影响。使用商业试剂盒检测氧化应激、一氧化氮水平和炎症。采用蛋白质免疫印迹分析来测定SCI大鼠中p38丝裂原活化蛋白激酶(MAPK)的蛋白表达水平。积雪草苷有效地提高了SCI大鼠的Basso、Beattie和Bresnahan评分。在实验动物中观察到脊髓含水量、诱导型一氧化氮合酶(iNOS)水平、核因子κB p65亚基、肿瘤坏死因子α、白细胞介素(IL)-1β和IL-6活性显著降低。此外,在检测氧化应激相关参数时,在SCI大鼠模型中检测到丙二醛生成增加,超氧化物歧化酶、谷胱甘肽和谷胱甘肽过氧化物酶水平降低。积雪草苷还显著抑制p38-MAPK的表达,这表明积雪草苷的治疗作用可能与p38-MAPK通路有关。这些数据证实,积雪草苷通过抗氧化和抗炎作用以及抑制p38-MAPK机制减轻SCI。

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