肾脏功能稳态和损伤的生物钟调节机制

The kidneys play a pivotal role in maintaining fluid and electrolyte balance, blood pressure regulation and metabolic homeostasis in the body. These essential functions are intricately regulated by the circadian clock, an internal timekeeping system that aligns physiological processes with the 24-hour day-night cycle. Growing evidence has demonstrated that most renal physiological processes, including renal blood flow, glomerular filtration, tubular reabsorption, hormone secretion, among others, exhibit circadian fluctuations, underscoring the critical role of the circadian clock in maintaining normal renal function. Core clock genes, such as Bmal1, Clock, Per, and Cry, serve as pivotal components of these regulatory mechanisms, orchestrating the temporal coordination of renal physiological processes. For instance, they regulate the expression and activity of key transporter proteins in the kidney, including Na⁺/H⁺ exchanger 3 (NHE3), epithelial Na⁺ channels (ENaC), aquaporin 2 (AQP2), as well as other critical molecules. Additionally, circadian clock proteins modulate the renin-angiotensin-aldosterone system and endothelin signaling pathways, which are master regulators of blood pressure homeostasis. Importantly, disruptions in circadian rhythms—triggered by shift work, lifestyle factors, environmental stressors, genetic mutations, disease states, and so on—are increasingly recognized as key contributors to adverse renal outcomes, manifesting as reduced glomerular filtration rate, impaired sodium handling, and disturbances in metabolic and homeostatic processes, ultimately elevating the risks of chronic kidney disease (CKD), acute kidney injury (AKI), hypertension, and associated cardiovascular complications. Conversely, kidney diseases like CKD and AKI can disrupt circadian rhythms, indicating a reciprocal interplay between renal dysfunction and circadian regulation. Understanding this complex interplay between the circadian clock and renal pathophysiology may pave the way for developing targeted interventions for kidney diseases. Emerging evidence has highlighted the potential benefits of maintaining a consistent circadian rhythm to optimize kidney function and protect against renal diseases, highlighting the importance of synchronizing biological clocks for renal health. Chronotherapy, the practice of aligning medical interventions with the body’s biological rhythms, has also shown promise in improving treatments for kidney-related conditions. This review aims to summarize recent advancements in understanding the role of the circadian clock in renal physiological homeostasis and disease progression, with a particular focus on the mechanisms by which core clock genes influence kidney injury. Advancing knowledge in this area is crucial for translating chronobiological insights into effective strategies for preventing and treating kidney diseases, ultimately improving renal health and enhancing overall quality of life.