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丁香叶提取物通过调控SIRT1/PGC-1α/NRF1信号通路改善急性胰腺炎大鼠肝损伤

Improvement of liver damage by clove leaf extracts in rats with acute pancreatitis regulated by SIRT1/PGC-1α/NRF1 signaling pathway

    摘要
  • 摘要:
      目的  探讨丁香叶提取物对急性胰腺炎（AP）大鼠肝组织的保护作用，以及沉默信息调节因子1（SIRT1）/过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）/核呼吸因子（NRF1）信号通路所发挥的作用。
      方法  将60只SD雄性大鼠随机分成对照组、AP组和低剂量、中剂量、高剂量组（低剂量、中剂量、高剂量丁香叶提取物），每组12只。除对照组外，其余各组大鼠均构建AP大鼠模型，并给予相应剂量的丁香叶提取物灌胃治疗。无菌条件下解剖大鼠，剥离肝脏，计算肝脏系数；检测血清中血清淀粉酶（AMY）、丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平；酶联免疫吸附测定（ELISA）检测血清炎性因子白细胞介素（IL）-6、肿瘤坏死因子-α（TNF-α）含量；检测肝脏组织氧化应激指标超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）；HE染色检测肝组织病理学变化；Western blot检测肝脏组织中SIRT1、PGC-1α、NRF1蛋白表达水平。
      结果  对照组大鼠肝脏组织结构正常；AP组大鼠肝脏组织结构损伤严重，且大量炎性细胞浸润；低剂量、中剂量、高剂量组大鼠肝脏组织病理损伤明显改善，炎性细胞浸润减少。与对照组相比，AP组大鼠肝脏系数及AMY、ALT、AST、IL-6、TNF-α、MDA水平升高（P < 0.05）；SOD和GSH-Px水平及SIRT1、PGC-1α、NRF1蛋白表达水平降低，差异有统计学意义（P < 0.05）。与AP组相比，低剂量、中剂量、高剂量组大鼠肝脏系数，AMY、ALT、AST、IL-6、TNF-α、MDA水平降低（P < 0.05）；SOD和GSH-Px水平及SIRT1、PGC-1α、NRF1蛋白表达水平升高，差异有统计学意义（P < 0.05）。
      结论  丁香叶提取物可能通过激活SIRT1/PGC-1α/NRF1信号通路，降低氧化应激和炎症反应，改善AP大鼠肝组织损伤。

     

    Abstract:
      Objective  To explore the protective effect of clove leaf extract on the liver tissue of acute pancreatitis (AP) rats, and the role of silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptorγ co-activator-1α (PGC-1α)/nuclear respiratory factor 1 (NRF1) signaling pathway.
      Methods  Sixty SD male rats were randomly divided into control group, AP group as well as low-dose, medium-dose and high-dose groups (low-dose, medium-dose and high-dose clove leaf extract), with twelve rats in each group. Except for the control group, rats in the other groups were all constructed AP rat models and given corresponding doses of clove leaf extract for intragastric treatment. The rat was dissected under aseptic conditions, the liver was stripped, and the liver coefficient was calculated; the serum amylase (AMY), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum were detected; the serum inflammatory factorsinterleukin (IL)-6 and tumor necrosis factor-α (TNF-α)contents were detected by enzyme-linked immunosorbent assay (ELISA) method; the oxidative stress indicators of liver tissueSuperoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were detected; the pathological changes of liver tissue were detected by HE staining; the protein expression levels of SIRT1, PGC-1α, and NRF1 in liver tissues were detected by Western blot.
      Results  The liver tissue structure of the rats in the control group was normal; the liver tissue structure of rats in the AP group was severely damaged, and a large number of inflammatory cells infiltrated; the liver tissue pathological damage of rats in the low-dose, medium-dose and high-dose groups was significantly improved, and the infiltration of inflammatory cells was reduced. Compared with the control group, the liver coefficients, AMY, ALT, AST, IL-6, TNF-α and MDA levels in the AP group increased significantly (P < 0.05); SOD and GSH-Px levels and SIRT1, PGC-1α and NRF1 protein expression levels reduced significantly (P < 0.05). Compared with the AP group, the liver coefficients, AMY, ALT, AST, IL-6, TNF-α and MDA levels in the low-dose, medium-dose and high-dose groups reduced significantly (P < 0.05); SOD and GSH-Px levels and SIRT1, PGC-1α, and NRF1 protein expression levels increased significantly (P < 0.05).
      Conclusion  Clove leaf extract may activate the SIRT1/PGC-1α/NRF1 signaling pathway, reduce oxidative stress and inflammation as well as improve liver tissue damage in AP rats.

     

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