靶向免疫中的神经反射回路以治疗肾脏疾病。
Targeting neural reflex circuits in immunity to treat kidney disease.
作者信息
Okusa Mark D, Rosin Diane L, Tracey Kevin J
机构信息
Division of Nephrology, Center for Immunity, Inflammation and Regenerative Medicine, PO Box 800133, 1300 Jefferson Park Avenue - West Complex, 5 th floor, Charlottesville, Virginia 22908-0133, USA.
Department of Pharmacology, PO Box 800735, 1304 Jefferson Park Avenue, University of Virginia, Charlottesville, Virginia 22908-0735, USA.
出版信息
Nat Rev Nephrol. 2017 Nov;13(11):669-680. doi: 10.1038/nrneph.2017.132. Epub 2017 Oct 3.
Neural pathways regulate immunity and inflammation via the inflammatory reflex and specific molecular targets can be modulated by stimulating neurons. Neuroimmunomodulation by nonpharmacological methods is emerging as a novel therapeutic strategy for inflammatory diseases, including kidney diseases and hypertension. Electrical stimulation of vagus neurons or treatment with pulsed ultrasound activates the cholinergic anti-inflammatory pathway (CAP) and protects mice from acute kidney injury (AKI). Direct innervation of the kidney, by afferent and efferent neurons, might have a role in modulating and responding to inflammation in various diseases, either locally or by providing feedback to regions of the central nervous system that are important in the inflammatory reflex pathway. Increased sympathetic drive to the kidney has a role in the pathogenesis of hypertension, and selective modulation of neuroimmune interactions in the kidney could potentially be more effective for lowering blood pressure and treating inflammatory kidney diseases than renal denervation. Use of optogenetic tools for selective stimulation of specific neurons has enabled the identification of neural circuits in the brain that modulate kidney function via activation of the CAP. In this Review we discuss evidence for a role of neural circuits in the control of renal inflammation as well as the therapeutic potential of targeting these circuits in the settings of AKI, kidney fibrosis and hypertension.
神经通路通过炎症反射调节免疫和炎症,并且特定分子靶点可通过刺激神经元进行调节。非药物方法的神经免疫调节正在成为包括肾脏疾病和高血压在内的炎症性疾病的一种新型治疗策略。电刺激迷走神经神经元或用脉冲超声治疗可激活胆碱能抗炎通路(CAP),并保护小鼠免受急性肾损伤(AKI)。肾传入神经和传出神经的直接支配可能在调节各种疾病的炎症以及对炎症做出反应中发挥作用,无论是在局部还是通过向炎症反射通路中重要的中枢神经系统区域提供反馈。肾脏交感神经驱动增加在高血压发病机制中起作用,并且与肾去神经支配相比,选择性调节肾脏中的神经免疫相互作用可能在降低血压和治疗炎症性肾脏疾病方面更有效。使用光遗传学工具选择性刺激特定神经元能够识别大脑中通过激活CAP调节肾功能的神经回路。在本综述中,我们讨论了神经回路在控制肾脏炎症中的作用证据,以及在急性肾损伤、肾纤维化和高血压背景下靶向这些回路的治疗潜力。