The role of neutrophils in producing hepatocellular dysfunction during the hyperdynamic stage of sepsis in rats
The role of neutrophils in producing hepatocellular dysfunction during the hyperdynamic stage of sepsis in rats
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DOI：
10.1006/jsre.1997.5216
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发表时间：
1997-12-01
影响因子：
2.2
通讯作者：
Chaudry, IH
中科院分区：
文献类型：
--
作者：
Molnar, RG;Wang, P;Chaudry, IH
尽管研究表明，脓毒症早期高动力阶段肝细胞功能受到抑制，但其机制仍不清楚。为了确定中性粒细胞是否在产生这种抑制中发挥作用，测量了患有败血症的中性粒细胞活性和中性粒细胞减少动物的肝细胞功能。在盲肠结扎和穿刺开始前 16 和 2 小时，通过尾静脉注射直接针对大鼠中性粒细胞的免疫球蛋白（抗中性粒细胞 Ig）诱导中性粒细胞减少症（CLP，即多种微生物败血症模型）。通过外周血涂片证实中性粒细胞减少症。中性粒细胞活性对照在脓毒症发作前给予未免疫的 Ig。假手术动物接受抗中性粒细胞 Ig 或对照 Ig。肝细胞功能[即吲哚菁绿清除的最大速度 (V-max) 和清除效率 (K-m)] 在 CLP（即早期高动力脓毒症）或假手术后 5 小时通过光纤导管和体内血液反射计测定。还测定了血清丙氨酸转氨酶（ALT）水平。结果表明，尽管 ALT 循环水平未升高，但脓毒症早期肝细胞功能显着下降。然而，V-max 和 K-m 的抑制可通过中性粒细胞耗竭来阻止，这表明中性粒细胞在这种条件下抑制肝细胞功能中发挥着不可或缺的作用。结果表明，在多种微生物脓毒症的早期阶段谨慎调节中性粒细胞功能可能有利于预防或延缓肝细胞功能障碍的发生。 (C) 1997 年学术出版社。
Although studies have shown that hepatocellular function is depressed during the early, hyperdynamic stage of sepsis, the mechanism responsible for this remains unknown. To determine whether neutrophils play any role in producing this depression, hepatocellular function was measured in neutrophil-competent and neutropenic animals subjected to sepsis. Neutropenia was induced by tail vein injection of an immuno-globulin directly against rat neutrophils (anti-neutrophil Ig) at 16 and 2 h prior to the initiation of cecal ligation and puncture (CLP, i.e., a model of polymicrobial sepsis). Neutropenia was confirmed by peripheral blood smears. Neutrophil-competent controls were given nonimmunized Ig before the onset of sepsis. Sham-operated animals received anti-neutrophil Ig or control Ig. Hepatocellular function [i.e., the maximal velocity of indocyanine green clearance (V-max) and efficiency of the clearance (K-m)] was determined by a fiber-optic catheter and in vivo hemoreflectometer at 5 h after CLP (i.e., early, hyperdynamic sepsis) or sham operation. Serum alanine aminotransferase (ALT) levels were also determined. The results indicate that although circulating levels of ALT were not elevated, hepatocellular function was significantly depressed during early sepsis. The depression in V-max and K-m was, however, prevented by neutrophil depletion, suggesting an integral role of the neutrophils in depressing hepatocellular function under such conditions. The results suggest that the prudent modulation of neutrophil function during the early stage of polymicrobial sepsis may be beneficial for preventing or delaying the occurrence of hepatocellular dysfunction. (C) 1997 Academic Press.