晶体液、高渗白蛋白和等渗白蛋白对实验性急性肺损伤肺肾损伤的影响。
Effects of crystalloid, hyper-oncotic albumin, and iso-oncotic albumin on lung and kidney damage in experimental acute lung injury.
机构信息
Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Centro de Ciências da Saúde, Avenida Carlos Chagas Filho, s/n, Bloco G-014, Ilha do Fundão, Rio de Janeiro, RJ, 21941-902, Brazil.
Department of Physiology and Pharmacology, Biomedical Institute, Fluminense Federal University, Rio de Janeiro, Brazil.
出版信息
Respir Res. 2019 Jul 16;20(1):155. doi: 10.1186/s12931-019-1115-x.
BACKGROUND
Conflicting data have reported beneficial effects of crystalloids, hyper-oncotic albumin (20%ALB), and iso-oncotic albumin (5%ALB) in critically ill patients. Although hyper-oncotic albumin may minimize lung injury, recent studies have shown that human albumin may lead to kidney damage proportional to albumin concentration. In this context, we compared the effects of Ringer's lactate (RL), 20%ALB, and 5%ALB, all titrated according to similar hemodynamic goals, on pulmonary function, lung and kidney histology, and molecular biology in experimental acute lung injury (ALI).
METHODS
Male Wistar rats received Escherichia coli lipopolysaccharide intratracheally (n = 24) to induce ALI. After 24 h, animals were anesthetized and randomly assigned to receive RL, 20%ALB, or 5%ALB (n = 6/group) to maintain hemodynamic stability (distensibility index of inferior vena cava < 25%, mean arterial pressure > 65 mmHg). Rats were then mechanically ventilated for 6 h. Six animals, which received neither ventilation nor fluids (NV), were used for molecular biology analyses.
RESULTS
The total fluid volume infused was higher in RL compared to 5%ALB and 20%ALB (median [interquartile range], 10.8[8.2-33.2] vs. 4.8[3.6-7.7] and 4.3[3.9-6.6] mL, respectively; p = 0.02 and p = 0.003). B-line counts on lung ultrasound (p < 0.0001 and p = 0.0002) and serum lactate levels (p = 0.01 and p = 0.01) were higher in RL than 5%ALB and 20%ALB. Diffuse alveolar damage score was lower in 5%ALB (10.5[8.5-12]) and 20%ALB (10.5[8.5-14]) than RL (16.5[12.5-20.5]) (p < 0.05 and p = 0.03, respectively), while acute kidney injury score was lower in 5%ALB (9.5[6.5-10]) than 20%ALB (18[15-28.5], p = 0.0006) and RL (16 [15-19], p = 0.04). In lung tissue, mRNA expression of interleukin (IL)-6 was higher in RL (59.1[10.4-129.3]) than in 5%ALB (27.0[7.8-49.7], p = 0.04) or 20%ALB (3.7[7.8-49.7], p = 0.03), and IL-6 protein levels were higher in RL than 5%ALB and 20%ALB (p = 0.026 and p = 0.021, respectively). In kidney tissue, mRNA expression and protein levels of kidney injury molecule (KIM)-1 were lower in 5%ALB than RL and 20%ALB, while nephronectin expression increased (p = 0.01 and p = 0.01), respectively.
CONCLUSIONS
In a rat model of ALI, both iso-oncotic and hyper-oncotic albumin solutions were associated with less lung injury compared to Ringer's lactate. However, hyper-oncotic albumin resulted in greater kidney damage than iso-oncotic albumin. This experimental study is a step towards future clinical designs.
背景
有研究表明晶体液、高渗白蛋白（20%ALB）和等渗白蛋白（5%ALB）对危重病患者有益，但数据相互矛盾。虽然高渗白蛋白可能会减轻肺损伤，但最近的研究表明白蛋白可能会导致与白蛋白浓度成正比的肾损伤。在这种情况下，我们比较了林格氏乳酸盐（RL）、20%ALB 和 5%ALB 的作用，所有这些都根据类似的血流动力学目标进行滴定，以观察它们对实验性急性肺损伤（ALI）的肺功能、肺和肾组织学以及分子生物学的影响。
方法
雄性 Wistar 大鼠经气管内给予大肠杆菌脂多糖以诱导 ALI。24 小时后，动物麻醉并随机分配接受 RL、20%ALB 或 5%ALB（每组 n = 6）以维持血流动力学稳定（下腔静脉扩张指数 < 25%，平均动脉压 > 65mmHg）。然后，大鼠接受机械通气 6 小时。6 只未接受通气或液体治疗的动物（NV）用于分子生物学分析。
结果
与 5%ALB 和 20%ALB 相比，RL 输注的总液体量更高（中位数[四分位距]，10.8[8.2-33.2]比 4.8[3.6-7.7]和 4.3[3.9-6.6]mL；p = 0.02 和 p = 0.003）。肺超声 B 线计数（p < 0.0001 和 p = 0.0002）和血清乳酸水平（p = 0.01 和 p = 0.01）在 RL 组高于 5%ALB 和 20%ALB 组。5%ALB（10.5[8.5-12]）和 20%ALB（10.5[8.5-14]）组的弥漫性肺泡损伤评分低于 RL 组（16.5[12.5-20.5]）（p < 0.05 和 p = 0.03），而急性肾损伤评分在 5%ALB 组（9.5[6.5-10]）低于 20%ALB 组（18[15-28.5]，p = 0.0006）和 RL 组（16[15-19]，p = 0.04）。在肺组织中，IL-6 的 mRNA 表达在 RL 组（59.1[10.4-129.3]）高于 5%ALB 组（27.0[7.8-49.7]，p = 0.04）或 20%ALB 组（3.7[7.8-49.7]，p = 0.03），RL 组的 IL-6 蛋白水平高于 5%ALB 和 20%ALB 组（p = 0.026 和 p = 0.021）。在肾组织中，5%ALB 组肾损伤分子（KIM）-1 的 mRNA 表达和蛋白水平低于 RL 组和 20%ALB 组，而肾小囊蛋白表达增加（p = 0.01 和 p = 0.01）。
结论
在 ALI 大鼠模型中，与 RL 相比，等渗和高渗白蛋白溶液与减轻肺损伤有关。然而，高渗白蛋白比等渗白蛋白导致更大的肾脏损伤。这项实验研究是未来临床设计的一个步骤。
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