Aksu Ugur, Demirci Cihan, Ince Can
Contrib Nephrol. 2011;174:119-128. doi: 10.1159/000329249. Epub 2011 Sep 9.
Despite the identification of several of the cellular mechanisms thought to underlie the development of acute kidney injury (AKI), the pathophysiology of AKI is still poorly understood. It is clear, however, that instead of a single mechanism being responsible for its etiology, AKI is associated with an entire orchestra of failing cellular mechanisms. Renal microcirculation is the physiological compartment where these mechanisms come together and exert their integrated deleterious action. Therefore, the study of renal microcirculation and the identification of the determinants of its function in models of AKI can be expected to provide insight into the pathogenesis and resolution of AKI. A major determinant of adequate organ function is the adequate oxygen (O(2)) supply at the microcirculatory level and utilization at mitochondrial levels for ATP production needed for performing organ function. The highly complex architecture of the renal microvasculature, the need to meet a high energy demand and the borderline hypoxemic nature of the kidney makes it an organ that is highly vulnerable to injury. Under normal, steady-state conditions, the oxygen supply to the renal tissues is well regulated and utilized not only for mitochondrial production of ATP (mainly for Na reabsorption), but also for the production of nitric oxide and the reactive oxygen species needed for physiological control of renal function. Under pathological conditions, such as inflammation, shock or sepsis, however, the renal microcirculation becomes compromised, which results in a disruption of the homeostasis of nitric oxide, reactive oxygen species, and oxygen supply and utilization. This imbalance results in these compounds exerting pathogenic effects, such as hypoxemia and oxidative stress, resulting in further deterioration of renal microcirculatory function. Our hypothesis is that this sequence of events underlies the development of AKI and that integrated therapeutic modalities targeting these pathogenic mechanisms will be effective therapeutic strategies in the clinical environment.
尽管已经确定了几种被认为是急性肾损伤（AKI）发生基础的细胞机制，但AKI的病理生理学仍未得到充分理解。然而，很明显，AKI并非由单一机制导致其病因，而是与一系列功能衰竭的细胞机制相关。肾微循环是这些机制共同作用并发挥综合有害作用的生理区域。因此，研究肾微循环并确定其在AKI模型中的功能决定因素，有望为深入了解AKI的发病机制和解决方法提供线索。器官功能正常的一个主要决定因素是微循环水平的充足氧气（O₂）供应以及线粒体水平对执行器官功能所需ATP产生的利用。肾微血管高度复杂的结构、满足高能量需求的必要性以及肾脏接近低氧血症的性质，使其成为一个极易受损的器官。在正常稳态条件下，肾脏组织的氧气供应受到良好调节，不仅用于线粒体产生ATP（主要用于钠重吸收），还用于产生一氧化氮和肾脏功能生理控制所需的活性氧。然而，在病理条件下，如炎症、休克或脓毒症，肾微循环会受到损害，导致一氧化氮、活性氧以及氧气供应和利用的稳态被破坏。这种失衡导致这些化合物发挥致病作用，如低氧血症和氧化应激，进而导致肾微循环功能进一步恶化。我们的假设是，这一系列事件是AKI发生的基础，针对这些致病机制的综合治疗方法将是临床环境中有效的治疗策略。
