NF-κB抑制剂PDTC对大鼠急性肺损伤中性粒细胞凋亡的影响

Influence of nuclear factor-κB inhibitor PDTC on polymorphonuclear neutrophil apoptosis in rats with acute lung injury

目的探讨NF-κB抑制剂吡咯烷二硫代氨基甲酸(PDTC),在脂多糖(LPS)所致大鼠急性肺损伤(ALI)中,对中性粒细胞(PMN)凋亡的影响。方法雄性大鼠54只,随机分3组,对照组(N组)6只,腹腔注射生理盐水3ml/kg;ALI组(L组)24只,腹腔注射LPS 3mg/kg;PDTC干预组(P+L组)24只,先腹腔注射PDTC 120mg/kg,30min后再腹腔注射LPS 3mg/kg,后两组分别于腹腔注射LPS后2、4、8、12h作为观测时间点,观察动脉血气分析、肺水含量测定(W/D)、支气管肺泡灌洗液(BALF)中PMN凋亡率。结果 L组PaO2较N组显著下降、P+L组PaO2降低较L组好转、L组和P+L组肺W/D均比N组明显增加、P+L组与L组比较2、4、8、12h显著减少、BALF中L组、P+L组PMN凋亡率比N组明显降低、P+L组PMN凋亡率增加,与相应时间点L各组相比较,差异均有统计学意义(P<0.05)。结论 PDTC通过促进PMN凋亡,可有效地减轻LPS所致大鼠ALI。

OBJECTIVE To explore the influence of nuclear factor-KB inhIbitor PDTC on the polymorphonuclear neutrophil（PMN） apoptosis in rats with acute lung injury（ALI） induced by lipopolysaccharide（LPS）.METHODS A total of 54 male rats were randomly divided into 3 groups.The rats in the control group N（n=6） were injected into the peritoneal cavity with 3 ml/kg of normal saline,ALI group（group L,n=24） were injected into peritoneal cavity with 3mg/kg of LPS;PDTC group（P plus L group,n=24） were firstly injected into peritoneal cavity with 120 mg/kg of PDTC,and then 3mg/kg of LPS at 30min after injecting with PDTC,the samples of the two groups were observed for the blood gas analysis,determination of lung water content（W/D）,and PMN apoptosis rate in bronchoalveolar lavage fluid（BALF） at 2h,4h,8h,and 12h after injecting with LPS.RESULTS As compared with group N,PaO2 decreased significantly in group L and was better in group P plus L（P〈0.05）.W/D increased more significantly in L and P plus L groups than group N,significantly decreasing in P plus L group as compared with group L;the apoptotic rate of PMN in BALF decreased more significantly in group L and group P plus L than group N,as compared with the apoptotic rate of PMN in BALF of group P plus L group and group L at corresponding time points,the difference was statistically significant（P〈0.05）.CONCLUSION PDTC can effectively relieve the ALI induced by LPS through promoting the apoptosis of PMN.