摘要
在过去的几十年中,证据积累表明副交感神经支配调节肝损伤和再生。肝脏通过迷走神经获得其副交感神经输入。在动物模型中,经常使用迷走神经刺激和横切来确定副交感神经输入对肝损伤反应的影响。这种策略对参与调节肝损伤的神经元机制提供了有限的理解。迷走神经的肝分支释放乙酰胆碱(ACh),其激活肝细胞中的毒蕈碱和烟碱受体以及非实质细胞以调节细胞功能。此外,迷走神经释放其他神经递质,如血管活性肠肽(VIP),它也调节肝脏损伤反应和血流动力学。因此,我们对利用迷走神经活动的模型中肝脏损伤后神经元调节的理解仍然有限。基因沉默技术和受体活性的药理操作不仅提高了我们对特定胆碱能受体作用的理解,而且还阐明了各种肝细胞亚群在调节肝损伤反应中的作用。随着器官和细胞特异性转基因小鼠的出现,我们对肝损伤神经调节的理解可能会进一步改善。本综述提供了对肝损伤胆碱能调节的最新理解,并指出了治疗肝损伤的潜在治疗靶点。
关键词: 肝损伤,副交感神经系统,毒蕈碱受体,烟碱受体。
图形摘要
Current Drug Targets
Title:Targeting Cholinergic System to Modulate Liver Injury
Volume: 19 Issue: 8
关键词: 肝损伤,副交感神经系统,毒蕈碱受体,烟碱受体。
摘要: Over the past few decades, evidence accumulated to indicate that parasympathetic innervation regulates liver injury and regeneration. Liver derives its parasympathetic input via vagus nerve. In animal models, vagus nerve stimulation and transection are frequently used to determine the impact of parasympathetic input on liver injury responses. Such strategies provide limited understanding of postneuronal mechanisms involved in the regulation of liver injury. The hepatic branch of vagus nerve releases acetylcholine (ACh), which activates muscarinic and nicotinic receptors in hepatocytes as well as non-parenchymal cells to modulate cellular functions. Moreover, vagus nerve releases other neurotransmitters such as vasoactive intestinal peptide (VIP), which also modulates liver injury responses and hemodynamics. Therefore, our understanding of the post-neuronal modulation of liver injury in models utilizing vagus nerve activity remains limited. Gene-silencing technologies and pharmacological manipulation of receptor activity have not only improved our understanding of the role of specific cholinergic receptors but also elucidated the role of various liver cell sub-populations in modulating liver injury response. With advent of organ- and cell-specific transgenic mice, our understanding of neural regulation of liver injury is likely to improve further. This review comprehensively provides current understanding of cholinergic regulation of liver injury, and points to potential therapeutic targets to treat liver injury.
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Cite this article as:
Targeting Cholinergic System to Modulate Liver Injury, Current Drug Targets 2018; 19 (8) . https://dx.doi.org/10.2174/1389450118666170619090219
DOI https://dx.doi.org/10.2174/1389450118666170619090219 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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