高级检索

    基于Nrf2/HO-1信号通路探讨迷迭香酸对急性胰腺炎大鼠氧化损伤的影响

    Effect of rosmarinic acid on oxidative damage in rats with acute pancreatitis based on the Nrf2/HO-1 signaling pathway

      摘要
    • 摘要: 目的：基于核因子E2相关因子2（Nrf2）/血红素加氧酶1（HO-1）信号通路探究迷迭香酸（RA）对急性胰腺炎（AP）大鼠氧化损伤的影响。方法：将40 只大鼠随机分为Sham 组、AP 组、RA 组、RA+ML385（Nrf2 抑制剂）组。采用酶联免疫吸附试验（ELISA）法检测各组大鼠血清淀粉酶（AMY）、脂肪酶（LIP）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）指标。HE染色检测胰腺组织病理学变化；TUNEL检测胰腺组织细胞凋亡；Western blotting和实时荧光定量PCR（RT-qPCR）法检测胰腺组织中Nrf2、HO-1蛋白和mRNA表达。结果：与Sham组相比，AP组血清中AMY、LIP、IL-1β、IL-6、TNF-α、MDA含量、胰腺指数、胰腺组织病理学评分和细胞凋亡率显著升高，血清中SOD活性、GSH-Px含量、胰腺组织中Nrf2、HO-1 mRNA及蛋白表达量降低（均P< 0.05）；与AP组相比，RA组血清中AMY、LIP、IL-1β、IL-6、TNF-α、MDA含量、胰腺指数、胰腺组织病理学评分和细胞凋亡率降低，血清中SOD活性、GSH-Px含量、胰腺组织中Nrf2、HO-1 mRNA及蛋白表达量显著升高（均P< 0.05）；RA+ML385组血清中AMY、LIP、IL-1β、IL-6、TNF-α、MDA含量、胰腺指数、胰腺组织病理学评分和细胞凋亡率高于RA组，血清中SOD活性、GSH-Px含量、胰腺组织中Nrf2、HO-1表达量低于RA组（均P< 0.05）。结论：RA可抑制AP大鼠炎症反应和氧化应激损伤，减轻胰腺组织病理损伤，其作用机制可能与激活Nrf2/HO-1信号通路有关。

       

      Abstract: Objective:To investigate the effect of rosmarinic acid (RA) on oxidative damage in rats with acute pancreatitis (AP) based on nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.Methods:A total of 40 rats were randomly divided into Sham group, AP group, RA group, and RA+ML385(Nrf2 inhibitor)group.The levels of serum amylase(AMY), lipase(LIP), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), malondialdehyde(MDA), superoxide dismutase(SOD), and glutathione peroxidase(GSH-Px)levels were measured by enzyme-linked immunosorbent assay(ELISA).Histopathological changes in pancreatic tissue were assessed using HE staining.Cell apoptosis in pancreatic tissue was detected using TUNEL assay.Protein expression and mRNA expression of Nrf2 and HO-1 in pancreatic tissue were examined using western blotting and real-time fluorescence quantitative PCR (RT-qPCR), respectively.Results:Compared with the Sham group, the levels of AMY, LIP, IL-1β, IL-6, TNF-α, MDA, pancreatic index, pancreatic histopathological score and cell apoptosis rate in the AP group significantly increased, while the activities of SOD, levels of GSH-Px, and protein and mRNA expression of Nrf2 and HO-1 in pancreatic tissue significantly decreased (P< 0.05).Compared with the AP group, the levels of AMY, LIP, IL-1β, IL-6, TNF-α, MDA, pancreatic index, pancreatic histopathological score, and cell apoptosis rate in the RA group decreased, while the activities of SOD, levels of GSH-Px, and protein and mRNA expression of Nrf2 and HO-1 in pancreatic tissue significantly increased(all P< 0.05).The RA+ML385 group showed higher levels of AMY, LIP, IL-1β, IL-6, TNF-α, MDA, pancreatic index, pancreatic histopathological score, and cell apoptosis rate compared with the RA group, while the activities of SOD, levels of GSH-Px, and protein and mRNA expression of Nrf2 and HO-1 in pancreatic tissue were lower than those in the RA group (all P< 0.05).Conclusion:RA can inhibit inflammation and oxidative damage in AP rats and alleviate pancreatic tissue pathological damage.Its mechanism of action may be related to the activation of the Nrf2/HO-1 signaling pathway.

       

      • HTML全文
      • 参考文献(12)
      • 相关文章
      • 施引文献
    • 资源附件(0)

    /

    返回文章
    返回