Kim Do Jin, Park Soo Hyun, Sheen Mee Rie, Jeon Un Sil, Kim Seung Whan, Koh Eun Suk, Woo Seung Kyoon
Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Respiration. 2006;73(6):815-24. doi: 10.1159/000095588. Epub 2006 Sep 5.
Acute renal failure (ARF) and acute respiratory distress syndrome (ARDS) coexist frequently, and the mortality rate of this combination is very high. It is well established that cytokines and chemokines play a major role in the pathogenesis of ARDS. In addition, heat shock proteins (HSPs) have been shown to be protective against ARDS.
The purpose of this study was to investigate the pathophysiology of ARDS in two different conditions, sepsis and ARF.
We examined five different rat animal models including sham-operated control, sepsis and three ARF models induced by renal ischemia/reperfusion injury, bilateral nephrectomy or bilateral ligation of renal pedicles. We analyzed pulmonary histology, pulmonary vascular permeability, cellular infiltration, and expression of cytokines, chemokines and HSPs.
Like sepsis, the three forms of ARF led to ARDS, as manifested by increased pulmonary vascular permeability and histological changes consistent with ARDS. On the other hand, ARF and sepsis differed in that ARF was associated with markedly lower levels of pulmonary cellular infiltration. Furthermore, while pulmonary expression of tumor necrosis factor-alpha increased in sepsis, cytokine-induced neutrophil chemoattractant 2 increased in nephrectomized rats indicating that different inflammatory mediators were involved in the injury mechanism. Finally, pulmonary expression of multiple HSPs including HSP27-1, HSP70, HSP70-4, HSP70-8 and HSP90 was significantly different between the two conditions.
We conclude that the pathophysiology of ARDS following ARF is distinct from that in sepsis. ARF-induced ARDS is characterized by a low level of cellular infiltration, induction of cytokine-induced neutrophil chemoattractant 2, and a discrete expression profile of HSPs.
急性肾衰竭（ARF）与急性呼吸窘迫综合征（ARDS）常同时存在，二者并存时死亡率很高。细胞因子和趋化因子在ARDS发病机制中起主要作用，这一点已得到充分证实。此外，热休克蛋白（HSPs）已被证明对ARDS具有保护作用。
本研究旨在探讨脓毒症和ARF这两种不同情况下ARDS的病理生理学。
我们检查了五种不同的大鼠动物模型，包括假手术对照组、脓毒症组以及由肾缺血/再灌注损伤、双侧肾切除或双侧肾蒂结扎诱导的三种ARF模型。我们分析了肺组织学、肺血管通透性、细胞浸润以及细胞因子、趋化因子和HSPs的表达。
与脓毒症一样，三种形式的ARF均导致ARDS，表现为肺血管通透性增加以及与ARDS一致的组织学变化。另一方面，ARF和脓毒症的不同之处在于，ARF相关的肺细胞浸润水平明显较低。此外，虽然脓毒症时肺肿瘤坏死因子-α表达增加，但肾切除大鼠中细胞因子诱导的中性粒细胞趋化因子2增加，表明不同的炎症介质参与了损伤机制。最后，两种情况下包括HSP27-1、HSP70、HSP70-4、HSP70-8和HSP90在内的多种HSPs的肺表达存在显著差异。
我们得出结论，ARF后ARDS的病理生理学与脓毒症不同。ARF诱导的ARDS的特征是细胞浸润水平低、细胞因子诱导的中性粒细胞趋化因子2的诱导以及HSPs的离散表达谱。
