氯胺酮和乌司他丁对急性肺损伤大鼠肺泡表面活性物质的影响

Effects of ketamine and ulinastatin on pulmonary surfactants in endotoxin-induced acute lung injury rats

目的:探讨氯胺酮、乌司他丁对急性肺损伤(ALI)的保护作用及其可能机制.方法:60只SD大鼠随机分至5组:氯胺酮组(K组)、乌司他丁组(U组)、氯胺酮+乌司他丁组(K+U组)、模型对照组(LPS组)和空白对照组(C组).采用内毒素(LPS)二次打击法建立ALI大鼠模型后,在2h和4h两个时间点上,每组随机取6只大鼠,检测PaO2、肺泡灌洗液(BALF)中磷脂和SP-A浓度,肺组织的湿/干重比值(W/D)以及HE染色.结果:LPS组PaO2、磷脂及SP-A浓度与其它4组相比最低(P<0.05),肺组织W/D比值最大(P<0.05).K组和U组的各指标在各个时间点均无统计学意义(P>0.05),但是均优于LPS组(P<0.05).C组的各指标在各个时间点上均最佳(P<0.05),并均保持平稳.K+U组次之,并与K组、U组相比各指标差异有统计学意义(P<0.05).各组PaO2、磷脂浓度、SP-A浓度在4h内均逐渐降低,但差异无统计学意义.PaO2与BALF中的磷脂浓度、SP-A浓度均呈高度线性相关性(P<0.01).结论:氯胺酮和乌司他丁均可有效减少ALI过程中肺泡表面活性物质(PS)活性成分SP-A和磷脂的丢失,从而改善PaO2,对ALI有显著的保护作用.两者联合应用效果更佳.

AIM：To investigate the protective effects of ketamine and ulinastatin on acute lung injury. METHODS：Sixty Sprague-Dawley rats were randomly divided into 5 groups in average：Ketamine（K） group,Ulinastatin（U） group,K＋U group,LPS group and the control group. The ALI models in the front 4 groups were manipulated by twice beats of LPS. Partial pressure of oxygen in artery （PaO2）,and the phosphatidylcholine and surfactant protein A（SP-A） in the bronchoalveolar lavage fluid（BALF） were assayed at 2 and 4 h. Wet/dryweight ratio（W/D）and histopathology were observed, too. RESULTS ： Compared with the other groups, the levels of PaOz, phosphatidylcholine and SP-A in the LPS group were the lowest （ P 〈 0.05 ）, and the ratio of W/D was the highest （ P 〈 0.05 ）. There was no significant statistic difference of the indexes between the K group and the U group （ P 〉 0.05 ）, but better than the LPS group （ P 〈 0.05）. All the indexes were the best and stable in the C group and that in the K ＋ U group were just inferior than those （ P 〈 0.05）. In all the groups, except of the C group, PaO2, phosphatidylcholine and SP-A decreased gradually from 2 to 4 hours after the models were set up. PaO2 was correlated with the concentration of phosphatidylcholine and SP-A in BALF in a high degree （P 〈 0. 01 ）. CONCLUSION： Both of Ketamine and Ulinastatin could inhibit the deduction of SP-A and phosphatidyl- choline and improve PaO2. Applying them in combination may obtain better protective effect in ALI.