氯胺酮对内毒素性急性呼吸窘迫综合征大鼠肺组织肿瘤坏死因子-α表达的影响

目的探讨氯胺酮对内毒素致伤急性呼吸窘迫综合征（ARDS）大鼠的防治作用和可能机制。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^-1LPS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1、2、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，测定BALF中白蛋白含量的变化以及肺组织中MPO活力的变化，ELISA法检测肺组织匀浆TNF-α含量的改变。结果L组和L＋K组气管内滴注LPS后PaO2／FiO2逐渐下降，在ARDS时、ARDS后1、2、3h较基础值显著降低（P〈0．01）。L组白蛋白含量、MPO活性及TNF-α含量较C组显著升高（P〈0．01）；与L组相比，L＋K组白蛋白含量、MPO活性及TNF-α含量则显著降低（P〈0．01，P〈0．05）。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。氯胺酮干预后可减少ARDS大鼠肺组织白蛋白渗出，降低MPO的活力和TNF-α含量。结论氯胺酮可能通过抑制TNF-α mRNA的表达，减少肺组织中TNF-α产生而对ARDS产生一定影响。

Effect of Ketamine on the Expression of TNF-a from Lung Tissues in Rats with LPS-Induced ARDS

Objective To investigate the preventive effect and possible mechanism of ketamine on rats with LPS - induced ARDS. Methods The rat model of ARDS was produced by intratracheal instillation of LPS （ 3.0 mg/kg） 16 h after intraperitoneal injection of endotoxine （ LPS, 1.0 mg/kg）. 32 male rats were randomly divided into 4 groups： saline group （ group C）, LPS group （ group L）, ketamine group （ group K） and LPS ＋ ket amine group （group L ＋ K）. Oxygenation index （PaO2/FiO2）, MAP and CVP were measured before instillation of LPS （baseline）, 0 h, 1 h, 2 h and 3 h after ARDS. Rats were killed 3 h after ARDS. Histological examina- tion was taken in the up lobe of right lung. The content of albumin, MPO activity and the content of TNF -α were measured in left lung. Results PaO2/FiO2 after ARDS was significantly lower than the baseline in the group L and L ＋ K. Albumin content, MPO activity and TNF -α content in the group L were much higher than those in group C. But albumin content, MPO activity and TNF -α content were significantly lower in group L ＋ K as compared with those in group L. Histological examination： treatment with ketamine attenuated the lung in-jury in ARDS rats. Conclusion Ketamine can attenuate LPS - induced ARDS in rats by inhibiting the expression of TNF - α mRNA and decreasing TNF - α production.