Jiang Haochen, Shang Zhi, You Liping, Zhang Jinghao, Jiao Junzhe, Qian Yihan, Lin Jiacheng, Wang Fang, Gao Yueqiu, Kong Xiaoni, Sun Xuehua
Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Central Laboratory, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
J Inflamm Res. 2023 Apr 17;16:1595-1610. doi: 10.2147/JIR.S404087. eCollection 2023.
Current pharmacological approaches to prevent hepatic ischemia/reperfusion injury (IRI) are limited. To mitigate hepatic injury, more research is needed to improve the understanding of hepatic IRI. Depending on traditional Chinese medicine (TCM) theory, acupuncture therapy has been used for the treatment of ischemic diseases with good efficacy. However, the efficacy and mechanism of acupuncture for hepatic IRI are still unclear.
Blood provided to the left and middle lobe of mice livers was blocked with a non-invasive clamp and then the clamps were removed for reperfusion to establish a liver IRI model. Quantitative proteomics approach was used to evaluate the impact of EA pretreatment on liver tissue proteome in the IRI group. Serum biochemistry was used to detect liver injury, inflammation, and oxidative stress levels. H&E staining and TUNEL staining were used to detect hepatocyte injury and apoptosis. Immunohistochemistry and ELISA were used to detect the degree of inflammatory cell infiltration and the level of inflammation. The anti-inflammatory and antioxidant capacities were detected by Quantitative RT-PCR and Western blotting.
We found that EA at Zusanli (ST36) has a protective effect on hepatic IRI in mice by alleviating oxidative stress, hepatocyte death, and inflammation response. Nuclear factor E2-related factor 2 (Nrf2) as a crucial target was regulated by EA and was then successfully validated. The Nrf2 inhibitor ML385 and cervical vagotomy eliminated the protective effect in the EA treatment group.
This study firstly demonstrated that EA pretreatment at ST36 significantly ameliorates hepatic IRI in mice by inhibiting oxidative stress via activating the Nrf2 signal pathway, which was vagus nerve-dependent.
目前预防肝缺血/再灌注损伤（IRI）的药理学方法有限。为减轻肝损伤，需要更多研究以增进对肝IRI的理解。根据中医理论，针刺疗法已用于治疗缺血性疾病且疗效良好。然而，针刺治疗肝IRI的疗效和机制仍不明确。
用无创夹阻断小鼠肝脏左叶和中叶的血流，然后移除夹子进行再灌注，以建立肝IRI模型。采用定量蛋白质组学方法评估电针预处理对IRI组肝组织蛋白质组的影响。采用血清生化检测肝损伤、炎症和氧化应激水平。采用苏木精-伊红（H&E）染色和末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）染色检测肝细胞损伤和凋亡。采用免疫组织化学和酶联免疫吸附测定（ELISA）检测炎症细胞浸润程度和炎症水平。通过定量逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测抗炎和抗氧化能力。
我们发现足三里（ST36）电针对小鼠肝IRI具有保护作用，可减轻氧化应激、肝细胞死亡和炎症反应。核因子E2相关因子2（Nrf2）作为关键靶点受电针调控，并随后得到成功验证。Nrf2抑制剂ML385和颈迷走神经切断消除了电针治疗组的保护作用。
本研究首次证明，ST36电针预处理通过激活Nrf2信号通路抑制氧化应激，显著改善小鼠肝IRI，且该作用依赖于迷走神经。
