Biochemistry and Molecular Biology and †Medicine, Division of Nephrology, Hypertension and Renal Transplantation, University of Florida, Gainesville, Florida 32610, USA.
J Am Soc Nephrol. 2011 Apr;22(4):598-604. doi: 10.1681/ASN.2010080803. Epub 2011 Mar 24.
Circadian variations in renal function were first described in the 19th century, and GFR, renal blood flow, urine production, and electrolyte excretion exhibit daily oscillations. These clinical observations are well established, but the underlying mechanisms that govern circadian fluctuations in kidney are not fully understood. Here we provide a brief overview of the machinery governing the circadian clock and examine the clinical and molecular evidence supporting a critical role for circadian rhythm in the kidney. There is a connection between BP oscillation and renal disease that supports the use of chronotherapy in the treatment of hypertension or correction of nondipping BP. Such studies support a developing model of clock controlled sodium and water transport in renal epithelial cells. Recent advances in identifying novel clock-controlled genes using rodent and cellular models also shed light on the molecular mechanisms by which the circadian clock controls renal function; however, the field is new and much more work remains.
肾功能的昼夜变化最早在 19 世纪就有描述,肾小球滤过率(GFR)、肾血流量、尿生成和电解质排泄都呈现出每日波动。这些临床观察已经得到充分证实,但调控肾脏昼夜波动的潜在机制尚不完全清楚。本文简要概述了调控昼夜节律钟的机制,并探讨了支持昼夜节律在肾脏中起关键作用的临床和分子证据。血压波动与肾脏疾病之间存在关联,这支持在高血压治疗或纠正非杓型血压时采用时间治疗学。这些研究支持了时钟控制的肾脏上皮细胞中钠和水转运的模型。利用啮齿动物和细胞模型来识别新的时钟控制基因的最新进展也揭示了昼夜节律钟调控肾脏功能的分子机制,但该领域尚处于起步阶段,还有很多工作要做。