CAJ | 학술논문

目的探讨利多卡因对脓毒症大鼠肺组织高迁移率族蛋白B1( HMGB1) mRNA表达的影响.方法雄性Wistar大鼠50只,体重200 ～ 250 g,采用随机数字表法,将其随机分为5组(n＝10):假手术组(S组)、脓毒症组(L组)、低、中和高剂量利多卡因组(LL1组、LL2组和LL3组).除S组外,其他4组采用盲肠结扎穿孔术制备大鼠脓毒症诱发急性肺损伤模型.LL1组、LL2组和LL3组分别于术毕、术后1、2h时腹腔注射利多卡因5、10、20 mg/kg,S组和L组给予等容量生理盐水.分别于术后24、48 h时处死5只大鼠,取肺组织,测定HMGB1 mRNA表达、髓过氧化物酶(MPO)活性和NF-κB活性,光镜下观察肺组织病理学结果.结果与S组比较,其他4组肺组织HMGB1 mRNA表达上调,MPO活性升高(P<0.05)；与L组比较,LL1组、LL2组和LL3组肺组织HMGB1 mRNA表达下调,MPO活性降低(P<0.01)；LL1组、LL2组和LL3组肺组织HMGB1 mRNA表达依次下调,MPO活性依次降低(P<0.05).LL1组、屿LL2和LL3组肺组织NF-κB活性逐渐降低,肺组织损伤程度逐渐减轻.结论利多卡因减轻脓毒症大鼠急性肺损伤的机制与下调肺组织HMGB1基因表达有关,其下调HMGB1基因表达的机制与抑制NF-κB活化有关.
목적 탐토리다잡인대농독증대서폐조직고천이솔족단백B1( HMGB1) mRNA표체적영향.방법 웅성Wistar대서50지,체중200 ～ 250 g,채용수궤수자표법,장기수궤분위5조(n＝10):가수술조(S조)、농독증조(L조)、저、중화고제량리다잡인조(LL1조、LL2조화LL3조).제S조외,기타4조채용맹장결찰천공술제비대서농독증유발급성폐손상모형.LL1조、LL2조화LL3조분별우술필、술후1、2h시복강주사리다잡인5、10、20 mg/kg,S조화L조급여등용량생리염수.분별우술후24、48 h시처사5지대서,취폐조직,측정HMGB1 mRNA표체、수과양화물매(MPO)활성화NF-κB활성,광경하관찰폐조직병이학결과.결과 여S조비교,기타4조폐조직HMGB1 mRNA표체상조,MPO활성승고(P<0.05)；여L조비교,LL1조、LL2조화LL3조폐조직HMGB1 mRNA표체하조,MPO활성강저(P<0.01)；LL1조、LL2조화LL3조폐조직HMGB1 mRNA표체의차하조,MPO활성의차강저(P<0.05).LL1조、서LL2화LL3조폐조직NF-κB활성축점강저,폐조직손상정도축점감경.결론 리다잡인감경농독증대서급성폐손상적궤제여하조폐조직HMGB1기인표체유관,기하조HMGB1기인표체적궤제여억제NF-κB활화유관.
Objective To investigate the effect of lidocaine on expression of high mobility group box 1 ( HMGB1 ) mRNA in lung tissue in septic rats.Methods Fifty male Wistar rats weighing 200-250 g were randomly divided into 5 groups ( n ＝ 10 each):group sham operation( group S) ; group sepsis( group L) ; group low,medium and high dose lidocaine (groups LL1,LL2,LL3 ).Sepsis was induced by cecal ligation and puncture in groups L,LL1,LL2,LL3.Lidocaine 5,10 and 20 mg/kg were injected intraperitoneally at the end of operation,and at 1 and 2 h after operation in groups LL1,LL2 and LL3.Five animals in each group were sacrificed at 24 and 48 h after operation respectively.The lungs were removed for microscopic examination and determination of HMGB1 mRNA expression,MPO activity and activation of NF-cB.Results Sepsis up-regulated HMGB1 mRNA and increased MPO activity and activation of NF-κB and induced lung histo-pathological damage.Lidocaine attenuated the abovementioned sepsis-induced changes in a dose-dependent manner.Conclusion Lidocaine can attenuate sepsis-induced acute lung injury by down-regulating HMGB1 mRNA expression and inhibiting activation of NF-κB.