Zhou Heng, Xu Ju-Ling, Huang San-Xiong, He Ying, He Xiao-Wei, Lu Sheng, Yao Bin
Department of Pharmacy, The First People's Hospital of Huzhou, First Affiliated Hospital of Huzhou University, Huzhou 313000, Zhejiang Province, China.
Department of Medicine, Medical School of Huzhou University, Huzhou 313000, Zhejiang Province, China.
World J Gastrointest Surg. 2023 Dec 27;15(12):2866-2878. doi: 10.4240/wjgs.v15.i12.2866.
Rapid regeneration of the residual liver is one of the key determinants of successful partial hepatectomy (PHx). At present, there is a lack of recognized safe, effective, and stable drugs to promote liver regeneration. It has been reported that vagus nerve signaling is beneficial to liver regeneration, but the potential mechanism at play here is not fully understood.
To explore the effect and mechanism of hepatic vagus nerve in liver regeneration after PHx.
A PHx plus hepatic vagotomy (Hv) mouse model was established. The effect of Hv on liver regeneration after PHx was determined by comparing the liver regeneration levels of the PHx-Hv group and the PHx-sham group mice. In order to further investigate the role of interleukin (IL)-22 in liver regeneration inhibition mediated by Hv, the levels of IL-22 in the PHx-Hv group and the PHx-sham group was measured. The degree of liver injury in the PHx-Hv group and the PHx-sham group mice was detected to determine the role of the hepatic vagus nerve in liver injury after PHx.
Compared to control-group mice, Hv mice showed severe liver injury and weakened liver regeneration after PHx. Further research found that Hv downregulates the production of IL-22 induced by PHx and blocks activation of the signal transducer and activator of transcription 3 (STAT3) pathway then reduces the expression of various mitogenic and anti-apoptotic proteins after PHx. Exogenous IL-22 reverses the inhibition of liver regeneration induced by Hv and alleviates liver injury, while treatment with IL-22 binding protein (an inhibitor of IL-22 signaling) reduce the concentration of IL-22 induced by PHx, inhibits the activation of the STAT3 signaling pathway in the liver after PHx, thereby hindering liver regeneration and aggravating liver injury in PHx-sham mice.
Hv attenuates liver regeneration after hepatectomy, and the mechanism may be related to the fact that Hv downregulates the production of IL-22, then blocks activation of the STAT3 pathway.
残肝的快速再生是成功实施部分肝切除术（PHx）的关键决定因素之一。目前，缺乏公认的安全、有效且稳定的促进肝再生的药物。据报道，迷走神经信号传导有利于肝再生，但其中潜在的机制尚未完全明确。
探讨肝迷走神经在PHx后肝再生中的作用及机制。
建立PHx加肝迷走神经切断术（Hv）的小鼠模型。通过比较PHx-Hv组和PHx-假手术组小鼠的肝再生水平，确定Hv对PHx后肝再生的影响。为进一步研究白细胞介素（IL）-22在Hv介导的肝再生抑制中的作用，检测PHx-Hv组和PHx-假手术组中IL-22的水平。检测PHx-Hv组和PHx-假手术组小鼠的肝损伤程度，以确定肝迷走神经在PHx后肝损伤中的作用。
与对照组小鼠相比，Hv小鼠在PHx后表现出严重的肝损伤且肝再生减弱。进一步研究发现，Hv下调PHx诱导的IL-22产生，并阻断信号转导和转录激活因子3（STAT3）通路的激活，进而降低PHx后各种促有丝分裂和抗凋亡蛋白的表达。外源性IL-22可逆转Hv诱导的肝再生抑制并减轻肝损伤，而用IL-22结合蛋白（IL-22信号抑制剂）处理可降低PHx诱导的IL-22浓度，抑制PHx后肝脏中STAT3信号通路的激活，从而阻碍PHx-假手术小鼠的肝再生并加重肝损伤。
Hv减弱肝切除术后的肝再生，其机制可能与Hv下调IL-22产生、进而阻断STAT3通路的激活有关。
