还原性谷胱甘肽对急性坏死性胰腺炎肺损伤的影响

Effect of reduced glutathione on lung injury in rats with acute necrotizing pancreatitis

目的:观察急性坏死性胰腺炎(ANP)大鼠肺组织核因子-κB(NF-κB) mRNA,细胞因子(TNF-α,IL-1β,IL-18),髓过氧化物酶(MPO)的变化,探讨还原性谷胱甘肽(GSH)治疗肺损伤的机制.方法:72只Wistar大鼠随机分成3组:ANP组,GSH组,SO组(假手术组).于术后6,12,18h取肺组织供实验用.免疫组化测定肺中IL-1β,IL-18,TNF-α的表达,比色法测定MPO的活性,RT-PCR检测NF-κBp65 mRNA的表达,胰、肺行组织学观察.结果:ANP组肺组织NF-κB mRNA,IL-18,IL-1β,TNF-α,MPO的水平升高,NF-κB,IL-1β,TNF-α在12h达高峰,与SO组相比各时间点均有统计学差异(P<0.05).GSH治疗后IL-1β,IL-18,TNF-α在各时间点均降低,NF-κB mRNA,MPO在12h降低(P<0.05).结论:ANP时NF-κB,IL-18,IL-1β,TNF-α及MPO均参与了肺损伤,GSH能够抑制肺NF-κB活化,促炎因子的表达及中性粒细胞的聚集,对肺损伤有保护作用.

AIM： To investigate the changes of transcription factor nuclear factor-κB （NF-κB）, TNF-α, IL-1β, IL-18, myeloperoxidase （MPO） in the lung of rats with acute necrotizing pancreatitis （ANP） and explore the effects of reduced glutathione （GSH） on lung injury. METHODS： Wistar rats （ n = 72 ） were divided into 3 groups at random, ANP group, GSH treated group, and sham operation （SO） group. Animals in the 3 groups were killed 6, 12 and 18 h after operations and lung tissue, pancreas tissue were harvested. The expressions of IL-18, IL-1β, TNF-α in lung tissue were measured by immunohistochemistry. MPO was determined by chromatometry. Intrapulmonary expression of NF- κBp65 mBNA was detected by RT-PCR. The histopathology of lung and pancreas was observed under the light microscope. RESULTS： The expressions of NF-κB mRNA, IL-18, IL-1β, TNF-α and the activity of MPO in lung tissue were much higher at 6, 12, 18 h in ANP group, with statistical significance compared with the SO group （ P 〈 0.05 ） and the levels of NF-κB mBNA, IL-1β and TNF-α reached the peak at 12 h. After treatment with GSH, the levels of IL-18, IL-1β, TNF-α became lower at 6, 12, 18 h and NF-κB mRNA, MPO were decreased at 12 h （P 〈0.05 vs ANP group）. CONCLUSION： All of NF-κB, TNF-α, IL- 1β, IL-18 and MPO have something to do with acute lung injury in experimental acute necrosis pancreatitis. GSH may inhibit the activity of NF-κB and neutrophil in lung tissue, decrease the con- centrations of inflammatory cytokines （ TNF-α, IL-1β, IL-18 ） , thus exerting the preventive effect against lung injury.