氯胺酮对内毒素诱导大鼠急性肺损伤的影响及其机制

目的探讨不同剂量氯胺酮对内毒素（LPS）诱导大鼠肺损伤的影响和作用机理。方法48只雄性Wistar大鼠随机分为4组：对照组，LPS组（5mg／kg），低剂量氯胺酮治疗组（5mg／kg），高剂量氯胺酮治疗组（10mg／kg），每组12只。建立内毒素诱导的大鼠急性肺损伤模型，于注射LPS后4h处死大鼠，测肺湿／干重比，观察支气管肺泡灌洗液（BALF）中性粒细胞计数比、蛋白浓度，测肺组织中肿瘤坏死因子α（TNF-α）、白细胞介素-8（IL-8）、NO水平。RT．PCR测肺组织中．NOSmRNA表达，Western-blot测肺组织中NF-κB蛋白表达。结果LPS组大鼠肺湿／干重比、BALF中性粒细胞计数比、蛋白浓度均明显增加（P〈0．01），肺组织中TNF-α、IL-8、NO水平显著性升高（P〈0.01），同时肺组织中iNOSmRNA和核因子-κB（NF-κB）蛋白表达均增加。而氯胺酮治疗组的各项指标均较LPS组减轻，大剂量组作用更明显。结论氯胺酮通过抑制NF-κB表达，减少炎症性细胞因子的产生，从而对内毒素（LPS）诱导的大鼠肺损伤有一定保护作用。

Protective effect of ketamine against acute rat lung injury induced by liopolysaccharide and its mechanism

OBJECTIVE: To investigate the protective effects of different concentrations of ketamine against acute lung injury induced by lipopolysaccharide (LPS) in rats and its mechanism. METHODS: Forty-eight male Wistar rats were randomized into 4 equal groups, namely the control group, LPS group, ketamine group I (5 mg/kg), and ketamine group II (10 mg/kg). The neutrophil count, protein contents in the bronchoalveolar lavage fluid (BALF) and the wet/dry lung weight ratio were measured 4 h after LPS injection. TNF-alpha, IL-8, NO, iNOS and NF-kappaB were also measured in the lung tissues. RESULTS: In LPS group, the neutrophil count, protein contents in BALF, the wet/dry lung weight ratio and the levels of tumor necrosis factor-alpha(TNF-alpha), interleukin-8 (IL-8), and NO were all significantly increased compared with the control group (P<0.01). The mRNA expression of iNOS and the protein expression of NF-kappaB were also increased in LPS groups. Ketamine treatment attenuated the increase in wet/dry lung weight ratio, neutrophil count, and protein contents in BALF in a dose-dependent manner. Ketamine also dose-dependently inhibited the production of TNF-alpha, IL-8 , and NO and lowered iNOS mRNA and NF-kappaB protein expression. CONCLUSION: Ketamine can offer protection against LPS-induced acute lung injury in rats by inhibiting the expression of NF-kappaB and attenuating the production of the inflammatory cytokines.