Hasegawa Sho, Inoue Tsuyoshi, Inagi Reiko
Division of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Division of CKD Pathophysiology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Kidney Res Clin Pract. 2019 Sep 30;38(3):282-294. doi: 10.23876/j.krcp.19.014.
The autonomic nervous system plays critical roles in maintaining homeostasis in humans, directly regulating inflammation by altering the activity of the immune system. The cholinergic anti-inflammatory pathway is a well-studied neuroimmune interaction involving the vagus nerve. CD4-positive T cells expressing β2 adrenergic receptors and macrophages expressing the alpha 7 subunit of the nicotinic acetylcholine receptor in the spleen receive neurotransmitters such as norepinephrine and acetylcholine and are key mediators of the cholinergic anti-inflammatory pathway. Recent studies have demonstrated that vagus nerve stimulation, ultrasound, and restraint stress elicit protective effects against renal ischemia-reperfusion injury. These protective effects are induced primarily via activation of the cholinergic anti-inflammatory pathway. In addition to these immunological roles, nervous systems are directly related to homeostasis of renal physiology. Whole-kidney three-dimensional visualization using the tissue clearing technique CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) has illustrated that renal sympathetic nerves are primarily distributed around arteries in the kidneys and denervated after ischemia-reperfusion injury. In contrast, artificial renal sympathetic denervation has a protective effect against kidney disease progression in murine models. Further studies are needed to elucidate how neural networks are involved in progression of kidney disease.
自主神经系统在维持人体稳态中发挥着关键作用，通过改变免疫系统的活性直接调节炎症。胆碱能抗炎途径是一种经过充分研究的涉及迷走神经的神经免疫相互作用。脾脏中表达β2肾上腺素能受体的CD4阳性T细胞和表达烟碱型乙酰胆碱受体α7亚基的巨噬细胞接收去甲肾上腺素和乙酰胆碱等神经递质，是胆碱能抗炎途径的关键介质。最近的研究表明，迷走神经刺激、超声和束缚应激对肾缺血再灌注损伤具有保护作用。这些保护作用主要通过激活胆碱能抗炎途径诱导产生。除了这些免疫作用外，神经系统还与肾脏生理的稳态直接相关。使用组织透明技术CUBIC（清晰、无障碍的脑/体成像鸡尾酒和计算分析）进行的全肾三维可视化显示，肾交感神经主要分布在肾脏的动脉周围，在缺血再灌注损伤后去神经支配。相反，人工肾交感神经去神经支配在小鼠模型中对肾脏疾病进展具有保护作用。需要进一步研究以阐明神经网络如何参与肾脏疾病的进展。
