Biochanin A与FGF21通过Nrf2信号通路对酒精中毒引起的肝损伤的保护作用及其机制研究

Alcohol poisoning after hepatitis viruses cause liver damage have become the second major cause. So far, the exact process and mechanism of alcohol-induced acute liver damage is not clear yet, and there is no satisfactory interventions including effective drug control. In the previous work, we found that Biochanin A inhibited the oxidative damage in the liver by activating the Nrf2 signaling pathway. In the meanwhile, we found that the lack of FGF21 may aggravate the liver damage. A great number of reports suggest that FGF21 also inhibits oxidative damage by activating the Nrf2 signaling pathway to protect the liver. Therefore, we speculate that the combination of Biochanin A and FGF21 may activate the Nrf2 signaling pathway more effectively to inhibit liver oxidative damage. In order to verify this hypothesis, the mice model of liver damage due to alcoholism is proposed to study the protective effects of Biochanin A and FGF21 on liver injury to clarify its pharmacological mechanism of protecting liver from injury and provide a scientific theoretical reference.

酒精中毒已经成为肝炎病毒后导致肝脏损伤的第二大病因。迄今为止酒精引起的急性肝损伤的确切发展过程和机制还不明确。也缺乏令人满意的干预包括有效的防治药物。前期工作中我们发现Biochanin A通过激活Nrf2信号通路从而抑制了肝脏内的氧化损伤;同时我们发现缺失的FGF21可以加重肝脏的损伤程度；大量的文献报道FGF21同样是通过激活Nrf2信号通路抑制氧化损伤来保护肝脏的。为此，我们推测Biochanin A与FGF21联合治疗可更有效的激活Nrf2信号通路抑制肝脏的氧化损伤。为了验证这一假说，本课题拟用C57BL,C57BL/Nrf2-null酒精中毒小鼠肝损伤模型，研究Biochanin A与FGF21对肝脏损伤的保护作用，阐明其保护肝脏损伤的药理机制，提供科学的理论依据。

酒精中毒已经成为肝炎病毒后导致肝脏损伤的第二大病因。迄今为止酒精引起的急性肝损伤的确切发展过程和机制还不明确。也缺乏令人满意的干预包括有效的防治药物。本次工作中我们通过构建的酒精中毒小鼠肝损伤模型，研究Biochanin A与FGF21对肝脏损伤的保护作用，阐明了其通过激活Nrf2信号通路从而抑制了肝脏内的氧化损伤保护肝脏损伤的药理机制，为酒精中毒引起的肝损伤提供了科学的理论依据，可以为今后肝损伤临床治疗突破性进展提供理论与实验依据。并且在该项目的进行中意外发现了中草药牛樟芝对肝脏的保护作用，同时发表了相关论文1篇，培养博士后1名、博士生1名、硕士研究生2名。