氯胺酮对内毒素诱导大鼠急性肺损伤的影响及其机制

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

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iNOS mRNA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iNOS mRNA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。

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 k＇etamine 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-α, IL-8, NO, iNOS and NF-κB 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-or （TNF-α）, interleukin-8 （IL-8）, and NO were allsignificantly increased compared with the control group （P〈0.01）. The mRNA expression of iNOS and the protein expression of NF-κB 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-α, IL-8, and NO and lowered iNOS mRNA and NF-κB protein expression. Conclusion Ketamine can offer protection against LPS-induced acute lung injury in rats by inhibiting the expression of NF-κB and attenuating the production of the inflammatory cytokines.