Yu Zhui, Ouyang Jing-Ping, Li Yin-Ping
Intensive Care Unit, Zhongnan Hospital of Wuhan University, 430071 Wuhan, China.
Clin Hemorheol Microcirc. 2009;41(2):117-25. doi: 10.3233/CH-2009-1162.
Application of glucocorticoids in sepsis or severe infection is disputable in clinic. In this experiment, we studied the effect of dexamethasone on nitric oxide synthases and whether dexamethasone could attenuate endotoxin-induced acute lung injury (ALI). SD rats received 5 mg/kg lipopolisaccharide (LPS) injection. Then arterial oxygen partial pressure (PaO2), lung histology, lung tissue nitric oxide (NO) production and expression of nitric oxide synthases (NOS) were detected at 0.5, 1, 2, 3 or 4 h after LPS injection. PaO2 and lung injury deteriorated upon time. Production of NO in lung tissue increased significantly particularly in the first two hours, and this change was mainly due to the over-expression of inducible NOS (iNOS), but not endothelial NOS (eNOS). Furthermore, a tight positive correlation was observed between lung injury score (LIS) and NO production level in lung tissue. Dexamethasone could ameliorate PaO2 and lung damage evidently, which were paralleled by significant decreases in the production of NO and in the expression of iNOS mRNA. In conclusion, dexamethasone could effectively attenuate endotoxin-induced lung injury through inhibiting iNOS expression and activation in the very early stage of ALI.
糖皮质激素在脓毒症或严重感染中的临床应用存在争议。在本实验中，我们研究了地塞米松对一氧化氮合酶的影响以及地塞米松是否能减轻内毒素诱导的急性肺损伤（ALI）。将脂多糖（LPS）以5mg/kg的剂量注射到SD大鼠体内。然后在注射LPS后的0.5、1、2、3或4小时检测动脉血氧分压（PaO2）、肺组织学、肺组织一氧化氮（NO）生成以及一氧化氮合酶（NOS）的表达。PaO2和肺损伤随时间恶化。肺组织中NO的生成显著增加，尤其是在前两小时，这种变化主要是由于诱导型NOS（iNOS）的过度表达，而非内皮型NOS（eNOS）。此外，肺损伤评分（LIS）与肺组织中NO生成水平之间存在紧密的正相关。地塞米松可明显改善PaO2和肺损伤，同时NO生成及iNOS mRNA表达显著降低。总之，地塞米松可通过在ALI极早期抑制iNOS的表达和激活来有效减轻内毒素诱导的肺损伤。
