氯胺酮对哮喘大鼠机械通气肺损伤的保护作用

目的：探讨氯胺酮对哮喘大鼠机械通气肺损伤的影响。方法：40只SD大鼠制备慢性哮喘模型后随机分成4组（n=10）：对照组（N组），哮喘大鼠旷置8h，不行机械通气；机械通气组（A组），采用容量控制机械通气模式（Vt=10ml／kg，f=30次／min）通气8h：不同剂量氯胺酮干预组（K1、K2组），机械通气前K1组静脉注射氯胺酮5mg／kg，K2组静脉注射氯胺酮10mg／kg，余同A组。实验结束后处死大鼠，测量肺湿干重比（W／D）及支气管肺泡灌洗液（BALF）中蛋白含量、白细胞（WBC）计数、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）及一氧化氮（NO）含量，观察肺组织病理形态学变化。结果：与N组比较，A组、K1组、K2组W／D增加，BALF中蛋白含量、白细胞计数、TNF-α、IL-6、NO含量增高（均P〈0．05），病理损伤程度加重；与A组比较，K1组、K2组W／D降低，BALF中蛋白含量、白细胞计数、TNF-α、IL-6、NO含量下降（均P〈0．05），病理损伤程度减轻；K2组蛋白含量、白细胞计数低于K1组（均P〈0．05），其余指标K1、K2两组间差异无显著性（P〉0．05）。结论：氯胺酮可抑制TNF-α、IL-6及NO的释放，从而对哮喘大鼠机械通气所致肺损伤起到保护作用。

Protective effect of ketamine on ventilation-induced lung injury in asthmatic rats

Objective：To investigate the effect of ketamine on ventilator-lnduced lung injury （VILI） in asthmatic rats. Methods： Forty Sprague-Dawley （SD） asthmatic rats were anesthetized, tracheotomized and randomly divided into four groups（n=10）： group N received normal saline iv. but not mechanically ventilation, the other three groups were ventilated for 8 h （Vt=10 ml/kg, f=30 bpm）. Group A received normal saline iv, group K1 received ketamine iv in a bolus of 5 mg/kg and group K2 received ketamine iv in a bolus of 10 mg/kg. The lungs were removed for determination of the wet to dry weight ratio （W/D）, TNF-α , IL-6, NO and protein content in bronchoalveolar lavage fluid （BALF）. Total white blood cells （WBC） in BALF were counted and lung histopathology were assessed among four groups. Results： The content of TNF-α, IL-6, NO, protein of BALF, together with the value of W/D were significantly higher in group A than that in group N, K1 and K2, while decreased in group K1 and K2 than that in, group A （P〈0.05）. A large quantity of WBC were found in BALF of group A, while the amount of WBC was decreased in group K1 and K2 than that in group A （P〈0.05）. Histopathologic findings demonstrated more infiltrating neutrophils and destructive changes of the alveolar wall in group A than that in other groups. The content of protein, the quantity of WBC in BALF were higher in group K1 than that in group K2, Conclusion： Long time ventilation can aggravate lung injury of asthma rats. Ketamine attenuates VILI in asthma rats in part because of probably inhibiting TNF-α, IL-6 and NO content in lung tissues.