氯胺酮对急性呼吸窘迫综合征大鼠肺组织iNOS活性及NO含量的影响

Effect of ketamine on iNOS activity and NO content in the lungs of ARDS rats

目的 探讨氯胺酮对内毒素性急性呼吸窘迫综合征 (ARDS)大鼠肺组织诱导型一氧化氮合酶 (iNOS)活性及一氧化氮 (NO)含量的影响。方法 采用大鼠腹腔注射 1.0mg·kg- 1 内毒素 (LPS) ,16h后在机械通气下气管内滴注 3.0mg·kg- 1 LPS的方法建立ARDS模型。雄性SD大鼠 34只 ,随机分为 4组 :内毒素组 (L组 ) ,生理盐水组(C组 ) ,内毒素加氯胺酮组 (L +K组 )及氯胺酮对照组 (K组 )。观察各组气管内滴注前 (基础值 ) ,达到ARDS时 ,ARDS后 1h、2h、3h各时间点氧合指数 (PaO2 FiO2 )、平均动脉压 (MAP)、中心静脉压 (CVP)的变化。于ARDS后 3h处死动物 ,取右肺上叶行肺形态学观察 ,左肺测定肺湿重 干重比 (W D) ,并测定肺组织匀浆中iNOS活性和NO含量的变化。结果 L组和L +K组气管内滴注LPS后PaO2 FiO2 逐渐下降 ,在ARDS时及ARDS后 1h、2h、3h较基础值显著降低 (P <0 .0 1)。L组W D、iNOS活性及NO含量较C组显著升高 (P <0 .0 1) ;与L组相比 ,L +K组W D、iNOS活性及NO含量则显著降低 (P <0 .0 1,P <0 .0 5 )。肺病理可见 :给予氯胺酮后 ,内毒素性ARDS大鼠肺组织损伤明显减轻。结论 氯胺酮明显减轻大鼠内毒素性ARDS ,其机制可能与通过抑制iNOS活性、降低NO含量有关。

Objective To investigate the effect of ketamine on iNOS activity and NO content in the lungs of rats with LPS-induced ARDS. Methods The rat model of ARDS was produced by intratracheal instillation of endotoxine (LPS, 3.0 mg/kg) 16 h after intraperitoneal injection of LPS 1.0 mg/kg. 32 male rats were randomly divided into 4 groups to proceed with different experiments: in control group (group C), norml saline was instilled into the trachea; in LPS group (group L), was made the ARDS model; in LPS + ketamine group (group L+K), ketamine 5 mg·kg -1·h -1 iv gtt was given along with intratracheal LPS; in ketamin control group (group K), ketamin iv was given the same way 2.5 h after the intatracheal instillation of LPS. Oxygenation index (PaO 2/FiO 2), MAP and CVP were measured before instillation of LPS (baseline) and 0 h, 1 h, 2 h and 3 h after the ARDS was established. The rats were sacrificed after 3 h of ARDS. Histological examination was made with the right lung. The left lung was used to determine the wet/dry weight ratio (W/D), the activity of iNOS and the content of NO. Results The PaO 2/FiO 2 after ARDS was significantly lower than the baseline in group L and group L+K. The W/D, iNOS activity and NO content were much higher in group L than in group C, but they were significantly lower in group L+K than in group L. Histological examination showed ketamine treatment attenuated the lung injury in ARDS rats. Conclusion Ketamine can attenuate LPS-induced ARDS in rats by inhibiting iNOS activity and decreasing NO production.