Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Department of Systems Pharmacology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan; PRESTO, Japan Science and Technology Agency (JST), Kawaguchi, Japan; Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research, Suita, Japan.
Kidney Int. 2019 Jul;96(1):129-138. doi: 10.1016/j.kint.2019.02.011. Epub 2019 Apr 9.
The sympathetic nervous system is critical in maintaining the homeostasis of renal functions. However, its three-dimensional (3D) structures in the kidney have not been elucidated due to limitation of conventional imaging methods. CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis) is a newly developed tissue-clearing technique, which enables whole-organ 3D imaging without thin-sectioning. Comprehensive 3D imaging by CUBIC found that sympathetic nerves are primarily distributed around arteries in the mouse kidney. Notably, the sympathetic innervation density was significantly decreased 10 days after ischemia-reperfusion injury (voluminal ratio of innervation area to kidney) by about 70%. Moreover, norepinephrine levels in kidney tissue (output of sympathetic nerves) were significantly reduced in injured kidneys by 77%, confirming sympathetic denervation after ischemia-reperfusion injury. Time-course imaging indicated that innervation partially recovered although overall denervation persisted 28 days after injury, indicating a continuous sympathetic nervous abnormality during the progression of chronic kidney disease. Thus, CUBIC-kidney, the 3D imaging analysis, can be a strong imaging tool, providing comprehensive, macroscopic perspectives for kidney research.
交感神经系统对于维持肾脏功能的稳态至关重要。然而，由于传统成像方法的限制，其在肾脏中的三维（3D）结构尚未阐明。CUBIC（透明、无阻碍的脑/体成像鸡尾酒和计算分析）是一种新开发的组织透明化技术，它可以实现无需切片的整个器官 3D 成像。通过 CUBIC 进行的全面 3D 成像发现，交感神经主要分布在小鼠肾脏的动脉周围。值得注意的是，缺血再灌注损伤后 10 天，交感神经支配密度（支配面积与肾脏的体积比）显著下降约 70%。此外，损伤肾脏组织中的去甲肾上腺素水平（交感神经的输出）降低了 77%，证实了缺血再灌注损伤后的交感神经去神经支配。时程成像表明，尽管在损伤后 28 天仍然存在整体去神经支配，但神经支配部分恢复，这表明在慢性肾脏病进展过程中存在持续的交感神经异常。因此，3D 成像分析的 CUBIC-肾脏可以成为一种强大的成像工具，为肾脏研究提供全面、宏观的视角。
