Chen Ying, Sun Haiyan, Huang Liyong, Li Juxiang, Zhou Wenke, Chang Jingling
College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China.
School of Life Science and Technology, Henan Institute of Science and Technology, Xinxiang, Henan 453003, China.
Evid Based Complement Alternat Med. 2015;2015:313657. doi: 10.1155/2015/313657. Epub 2015 May 18.
Redox homeostasis has been implicated in subarachnoid hemorrhage (SAH). As a result, antioxidants and/or free radical scavengers have become an important therapeutic modality. Considering that radix trichosanthis (RT) saponins exhibited strong antioxidant ability both in vivo and in vitro, the present study aimed to reveal whether the neuroprotective activities of RT saponins were mediated by p38/p53 signal pathway after SAH. An established SAH model was used and superoxide dismutase (SOD), malondialdehyde (MDA), induced nitric oxide synthase (iNOS), nitric oxide (NO), lactate dehydrogenase (LDH), p-p38, and p53 activation were detected after 48 h of SAH. The results showed that RT saponins inhibited iNOS expression to restore NO to basal level. Moreover, compared with Cu/Zn-SOD, RT saponins (2 mg/kg/d dosage) significantly increased Mn-SOD activity after SAH. Accompanied with lowered NO and elevated SOD, decreased p38 phosphorylation and p53 activities were observed, especially for RT saponins at 2 mg/kg/d dosage. In this setting, the neurological outcome was also improved with less neuronal cells damage after RT saponins pretreatment. Our findings demonstrated the beneficial effects of RT saponins in enhancing neuroprotective effects by deducing iNOS activity, normalizing SOD level, and inhibiting p-p38 and p53 expression, hence offering significant therapeutic implications for SAH.
氧化还原稳态与蛛网膜下腔出血(SAH)有关。因此,抗氧化剂和/或自由基清除剂已成为一种重要的治疗方式。鉴于天花粉(RT)皂苷在体内和体外均表现出较强的抗氧化能力,本研究旨在揭示SAH后RT皂苷的神经保护活性是否由p38/p53信号通路介导。采用已建立的SAH模型,在SAH 48小时后检测超氧化物歧化酶(SOD)、丙二醛(MDA)、诱导型一氧化氮合酶(iNOS)、一氧化氮(NO)、乳酸脱氢酶(LDH)、p-p38和p53的激活情况。结果表明,RT皂苷抑制iNOS表达,使NO恢复到基础水平。此外,与铜/锌超氧化物歧化酶相比,SAH后RT皂苷(剂量为2mg/kg/d)显著提高了锰超氧化物歧化酶的活性。伴随着NO降低和SOD升高,观察到p38磷酸化和p53活性降低,尤其是剂量为2mg/kg/d的RT皂苷。在此情况下,RT皂苷预处理后神经功能结局也得到改善,神经元细胞损伤减少。我们的研究结果表明,RT皂苷通过降低iNOS活性、使SOD水平正常化以及抑制p-p38和p53表达,在增强神经保护作用方面具有有益效果,因此为SAH提供了重要的治疗意义。