| 刘文晶,孙世杰,韩 冰,高 杰,董雅楠.槲皮素调节AMPK/SIRT1/NF-κB通路对乙型肝炎大鼠肝组织损伤的影响[J].现代生物医学进展英文版,2023,(4):624-629. |
| 槲皮素调节AMPK/SIRT1/NF-κB通路对乙型肝炎大鼠肝组织损伤的影响 |
| Impact of Quercetin on Liver Tissue Damage in Hepatitis B Rats by Regulating AMPK/SIRT1/NF-κB Pathway |
| Received:July 23, 2022 Revised:August 19, 2022 |
| DOI：10.13241/j.cnki.pmb.2023.04.005 |
| 中文关键词: 槲皮素 AMPK/SIRT1/NF-κB通路 乙型肝炎 肝组织损伤 炎症反应 |
| 英文关键词: Quercetin AMPK/SIRT1/NF-κB pathway Hepatitis B Liver tissue damage Inflammatory response |
| 基金项目:山东省医药卫生科技发展计划项目（2018WS065） |
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| 中文摘要: |
| 摘要 目的：探究槲皮素调节AMPK/SIRT1/NF-κB通路对乙型肝炎（HB）大鼠肝组织损伤的影响。方法：采用随机数字表法将65只Wistar大鼠分为Ctrl组、HB组、槲皮素低剂量组（槲皮素L组，50 mg/kg）、槲皮素高剂量组（槲皮素H组，200 mg/kg）及槲皮素H+AMPK抑制剂组（200 mg/kg槲皮素+10 mg/kg Compound C），每组各13只，采用尾静脉注射携带1.3拷贝HBV基因组的重组8型腺相关病毒（rAAV8-1.3HBV）法建立HB大鼠模型（Ctrl组除外）；酶联免疫吸附实验（Elisa）检测血清中HB表面抗原（HBsAg）、HB e抗原（HBeAg）、肝功能指标[谷丙转氨酶（ALT）、谷草转氨酶（AST）、总胆红素（TBIL）]水平及肝组织中炎性因子[白介素-1β（IL-1β）、肿瘤坏死因子α（TNF-α）]水平；实时荧光定量PCR（qRT-PCR）检测血清中HBV-DNA水平；苏木素-伊红（HE）染色、曼森氏（Masson）染色观察肝组织病理改变；免疫印迹法（WB）检测肝组织中AMPK/SIRT1/NF-κB通路蛋白表达水平。结果：与Ctrl组比较，HB组血清中HBsAg、HBeAg、HBV-DNA、ALT、AST、TBIL水平均升高（P<0.05）；肝组织可见肝静脉扩张、充血，肝细胞排列紊乱、水肿、坏死，同时发生明显纤维化；肝组织中AMPK磷酸化、SIRT1蛋白水平均降低，IL-1β、TNF-α水平及核NF-κB蛋白水平均升高；经槲皮素L、槲皮素H干预后上述情况均得到改善，且槲皮素H干预改善更明显（P<0.05）；而增加AMPK抑制剂干预后，槲皮素H干预的改善作用被削弱（P<0.05）。结论：槲皮素能够减轻HB大鼠肝组织损伤，保护其肝功能，其机制可能与调节AMPK/SIRT1/NF-κB通路有关。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the impact of quercetin regulating AMPK/SIRT1/NF-κB pathway on liver tissue damage in hepatitis B (HB) rats. Methods: 65 Wistar rats were divided into Ctrl group, HB group, Quercetin low-dose group (Quercetin L group, 50 mg/kg), Quercetin high-dose group (Quercetin H group, 200 mg/kg) and Quercetin H combined with AMPK inhibitor group (200 mg/kg Quercetin combined with 10 mg/kg Compound C) by random number table method, with 13 rats in each group, the HB rat model (except Ctrl group) was established by tail vein injection of recombinant adeno-associated virus type 8 (rAAV8-1.3HBV) carrying 1.3 copies of HBV genome. Enzyme-linked immunosorbent assay (Elisa) was used to detect serum levels of HB surface antigen (HBsAg), HB e antigen (HBeAg) and liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL)] and inflammatory factors [interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α)] in liver tissue. Real-time quantitative PCR (qRT-PCR) was used to detect the level of serum HBV-DNA. Hematoxylin-eosin (HE) staining and Masson (Masson) staining were used to observe the pathological changes of liver tissue. The protein expression of AMPK/SIRT1/NF-κB pathway in liver tissue was detected by Western blotting. Results: Compared with the Ctrl group, the serum levels of HBsAg, HBeAg, HBV-DNA, ALT, AST and TBIL in the HB group were increased (P<0.05). The liver tissue showed hepatic vein dilatation, congestion, disordered arrangement of liver cells, edema, necrosis, and obvious fibrosis. The phosphorylation of AMPK and the level of SIRT1 protein in liver tissue were decreased, the levels of IL-1β, TNF-α and nuclear NF-κB protein were increased. After Quercetin L and Quercetin H intervention, the above conditions were improved, and Quercetin H intervention improved more obviously (P<0.05). However, after the intervention of AMPK inhibitor, the improvement effect of Quercetin H intervention was weakened (P<0.05). Conclusion: Quercetin can alleviate liver tissue damage in HB rats, and protect liver function, and the mechanism may be related to the regulation of AMPK/SIRT1/NF-κB pathway. |
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