基于Nrf2/HO-1信号通路探讨虾青素对创伤性脑损伤模型大鼠氧化应激和炎症反应的影响 点击下载
| 论文标题： | 基于Nrf2/HO-1信号通路探讨虾青素对创伤性脑损伤模型大鼠氧化应激和炎症反应的影响 |
| 英文标题： | |
| 中文摘要： | 目的 探讨虾青素对创伤性脑损伤（TBI）大鼠氧化应激和炎症反应的影响。方法将雄性SD大鼠分为假手术组、模型组、虾青素低剂量组（20mg/kg）、虾青素高剂量组（40mg/kg）、虾青素+ML385组[虾青素40mg/kg+核转录因子红系2相关因子2（Nrf2）抑制剂ML38530mg/kg]，每组14只。除假手术组外，其余各组大鼠按改良的Feeney自由落体撞击法复制TBI大鼠模型。各药物组大鼠灌胃或腹腔注射相应药液，假手术组和模型组大鼠灌胃等体积生理盐水。分别于药物干预后第1、3、7天对各组大鼠的神经功能进行评分；于药物干预后第7天，观察各组大鼠脑组织形态学变化并进行炎症浸润评分，观察其脑组织神经细胞超微结构，检测脑组织中氧化应激指标[超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）、一氧化氮（NO）]、炎症反应指标[肿瘤坏死因子α、白细胞介素1β（IL-1β）、IL-6、诱导型一氧化氮合酶]含量和Nrf2、血红素加氧酶1（HO-1）、NAD（P）H醌氧化还原酶1（NQO1）蛋白及mRNA的表达情况。结果与假手术组比较，模型组大鼠脑组织水肿明显并伴有大量炎症细胞浸润，神经细胞的细胞器形态受损、数量减少且超微结构破损严重；其神经功能评分，脑组织中SOD、CAT、GSH-Px、NO含量和Nrf2、HO-1、NQO1蛋白及mRNA的相对表达水平均显著降低，炎症浸润评分、MDA含量和炎症反应指标含量均显著升高（P＜0.05）。与模型组比较，低、高剂量虾青素可显著改善脑组织及神经细胞的病理状态和神经功能评分（虾青素低剂量组药物干预第1天除外），可剂量依赖性地升高脑组织中SOD、CAT、GSH-Px、NO含量和Nrf2、HO-1、NQO1蛋白及mRNA的相对表达水平，降低炎症浸润评分、MDA含量和炎症反应指标含量（P＜0.05）；而ML385可显著抑制虾青素的上述作用（P＜0.05）。结论虾青素可能通过激活Nrf2/HO-1信号通路而减轻TBI大鼠的氧化应激，缓解其神经功能损伤，降低炎症反应水平。 |
| 英文摘要： | OBJECTIVE To investigate the effects of astaxanthin on oxidative stress and inflammatory reaction in rats with traumatic brain injury （TBI）. METHODS Male SD rats were randomly divided into sham operation group， model group， astaxanthin low-dose group （20 mg/kg）， astaxanthin high-dose group （40 mg/kg）， astaxanthin+ML385 group [astaxanthin 40 mg/kg+ nuclear factor-erythroid 2-related factor 2 （Nrf2） inhibitor ML385 30 mg/kg]， with 14 rats in each group. Except for the sham operation group， TBI model was induced by the modified Feeney free-fall impact method in other groups. The rats in each drug group were given the corresponding drug intragastrically or intraperitoneally， and the rats in the sham operation group and model group were intragastrically given a constant volume of normal saline. The neurological function of rats in each group was scored on the 1st， 3rd and 7th day after drug intervention； on the 7th day of drug intervention， the changes of cerebral histomorphology and inflammatory infiltration score were observed in each group， and the ultrastructure of nerve cells in brain tissue was also observed. The contents of oxidative stress indexes [superoxide dismutase （SOD）， catalase （CAT）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， nitric oxide （NO）] and inflammatory reaction indexes [tumor necrosis factor-α， interleukin-1β （IL-1β）， IL-6， inducible nitric oxide synthase] as well as protein and mRNA expressions of Nrf2， heme oxygenase-1 （HO-1） and NAD（P）H： quinone oxidoreductase 1 （NQO1） were detected in cerebral tissue. RESULTS Compared with the sham operation group， the brain edema of rats in the model group was obvious， accompanied by a large number of inflammatory cells infiltrated， the shape of organelles was damaged and their number was reduced， and the ultrastructure of nerve cells was seriously damaged. The neurological function score， the contents of SOD， CAT， GSH-Px and NO and the relative expression levels of Nrf2， HO-1 and NQO1 protein and mRNA in brain tissue were significantly decreased， while the inflammatory infiltration scores， the contents of MDA and inflammatory reaction indexes were significantly increased （P＜0.05）. Compared with the model group， low-dose and high-dose astaxanthin could significantly improve the pathological status of brain tissue and nerve cells and neurological function scores （except for the first day of drug intervention in the astaxanthin low-dose group）， increase the contents of SOD， CAT， GSH-Px and NO and the relative expression levels of Nrf2， HO-1， NQO1 protein and mRNA in brain tissue in a dose-dependent manner， and reduce inflammatory infiltration scores， the contents of MDA and inflammatory reaction indexes （P＜0.05）. ML385 could significantly inhibit the above effects of astaxanthin （P＜0.05）. CONCLUSIONS Astaxanthin may reduce the oxidative stress of TBI model rats， alleviate the neurological damage and reduce the level of inflammation reaction by activating the Nrf2/HO-1 signaling pathway. |
| 期刊： | 2023年第34卷第20期 |
| 作者： | 易宇光；刘昌平；何佳佳 |
| 英文作者： | YI Yuguang，LIU Changping，HE Jiajia |
| 关键字： | 虾青素；创伤性脑损伤；氧化应激；炎症反应；核转录因子红系2相关因子2/血红素加氧酶1信号通路 |
| KEYWORDS： | astaxanthin； traumatic brain injury； oxidative stress； inflammatory reaction； Nrf2/HO-1 signaling pathway |
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