全面三维分析（CUBIC-kidney）可显示缺血/再灌注损伤后异常的肾交感神经。
Comprehensive three-dimensional analysis (CUBIC-kidney) visualizes abnormal renal sympathetic nerves after ischemia/reperfusion injury.
机构信息
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.
出版信息
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。
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