Prevention of gram-negative translocation reduces the severity of hepatopulmonary syndrome
Prevention of gram-negative translocation reduces the severity of hepatopulmonary syndrome
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DOI：
10.1164/rccm.200201-027oc
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发表时间：
2002-08-15
影响因子：
24.7
通讯作者：
Hervé, P
中科院分区：
文献类型：
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作者：
Rabiller, A;Nunes, H;Hervé, P
肝肺综合征 (HPS) 的特点是肺内血管扩张和肺泡动脉氧差 (AaPo(2)) 增加。这些异常与肺一氧化氮（NO）生成增加有关，主要取决于肺血管内巨噬细胞内诱导型一氧化氮合酶（iNOS）的表达和活性的增加，以及较小程度的内皮型一氧化氮合酶（eNOS）的表达和活性的增加。肺血管内巨噬细胞产生 NOS 可能与肺循环中存在的易位肠道细菌有关。为了检验这一假设，我们确定了在胆总管结扎诱导的肝硬化大鼠中给予诺氟沙星 5 周以防止革兰氏阴性细菌易位后，巨噬细胞隔离、肺 NOS 表达和活性以及 HPS 严重程度是否有所降低。诺氟沙星将革兰氏阴性易位的发生率从 70% 降低至 0%，并将含有超过 10 个巨噬细胞的肺微血管百分比从 52 +/- 7% 降低至 21 +/- 8% (p < 0.01)。 AaPo(2) 和静脉内 Tc-99m 标记的白蛋白大聚集体的脑摄取（反映肺内血管扩张）与未经治疗的肝硬化和假手术大鼠相比处于中间水平。肺 iNOS（而非 eNOS）的活性和表达降至正常。诺氟沙星可以通过抑制革兰氏阴性细菌移位来降低 HPS 的严重程度，从而减少肺血管内巨噬细胞产生的 NO。细菌易位可能是HPS发病机制的关键。
Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary vascular dilatations and an increased alveoloarterial oxygen difference (AaPo(2)). These abnormalities are related to augmented pulmonary nitric oxide (NO) production, dependent primarily on increases in the expression and activity of inducible NO-synthase (iNOS) within pulmonary intravascular macrophages and, to a lesser extent, of endothelial NOS (eNOS). Production of NOS by pulmonary intravascular macrophages might be related to translocated gut bacteria present in the pulmonary circulation. To test this hypothesis, we determined whether macrophage sequestration, lung NOS expression and activity, and HPS severity were decreased after norfloxacin was given for 5 weeks to prevent Gram-negative bacterial translocation in rats with common bile duct ligation-induced cirrhosis. Norfloxacin decreased the incidence of Gram-negative translocation from 70 to 0% and the percentage of pulmonary microvessels containing more than 10 macrophages from 52 +/- 7 to 21 +/- 8% (p < 0.01). AaPo(2) and cerebral uptake of intravenous Tc-99m-labeled albumin macroaggregates (reflecting intrapulmonary vascular dilatations) were intermediate to those of untreated cirrhotic and sham-operated rats. The activity and expression of lung iNOS, but not eNOS, were reduced to normal. Norfloxacin may reduce HPS severity by inhibiting Gram-negative bacterial translocation, thereby decreasing NO production by pulmonary intravascular macrophages. Bacterial translocation may be the key to the pathogenesis of HPS.