N-乙酰半胱氨酸联合抗坏血酸对大鼠重症急性胰腺炎时急性肺损伤的作用

Effect of N-Acetylcysteine and Ascorbic Acid on Acute Lung Injury of Severe Acute Pancreatitis in Rats

目的:探讨N-乙酰半胱氨酸(NAC)联合抗坏血酸对大鼠重症急性胰腺炎(SAP)时急性肺损伤(ALI)的作用及机制。方法:40只SD大鼠随机分为假手术(SO)组、SAP+ALI组、NAC治疗组、NAC+抗坏血酸治疗组4组。采用胰胆管逆行注射4%的牛磺胆酸钠(0.1ml/100g)诱导SAP+ALI模型,NAC治疗组于造模后30min腹腔注射5%的NAC(0.2ml/100g),NAC+抗坏血酸治疗组造模后30min腹腔注射5%的NAC(0.2ml/100g)+5%的抗坏血酸(0.2ml/100g)。造模后12h取材,同时观察肺组织病理变化、肺组织湿/干重比率、大鼠血清丙二醛(MDA)、超氧化物歧化酶(SOD)、还原性谷光甘肽(GSH)、谷光甘肽过氧化物酶(GSH-PX)、肺组织髓过氧化物酶(MPO)及肺组织中核因子-κB(NF-κB)的表达。结果:SAP+ALI组肺组织湿/干重比率、肺组织病理损伤、MDA、MPO及NF-κB的表达明显高于其他3组(P<0.01),NAC治疗组或NAC+抗坏血酸治疗组这些指标显著低于SAP+ALI组(P<0.01),且NAC+抗坏血酸治疗组明显低于NAC治疗组(P<0.01),但均高于SO组(P<0.01);GSH、GSH-PX在SAP+ALI组明显低于其他3组(P<0.05),经NAC处理或NAC+抗坏血酸处理后这些指标明显增高,且NAC+抗坏血酸治疗组明显高于NAC治疗组(P<0.05),但均低于SO组(P<0.01);SOD在SAP+ALI组和NAC处理组无明显差异(P>0.05),但均低于SO组和NAC+抗坏血酸治疗组(P<0.01)。结论:NAC和抗坏血酸可抑制NF-κB的活化和减少氧自由基的产生,进而减轻了重症急性胰腺炎时肺组织的损伤和全身炎症反应综合征(SIRS),对重症急性胰腺炎时急性肺损伤具有重要的治疗和保护作用。

Objective：To investigate the effect and mechanism of N-acetylcysteine（NAC） and ascorbic acid on acute lung injury（ALI） of severe acute pancreatitis（SAP）.Methods：Forty SD rats were randomized into sham operation（SO） group,SAP＋ALI group,NAC treated group,and NAC＋ ascorbic acid treated group.The model of SAP＋ALI was induced by retrograde injection of 4% sodium taurocholate（0.1 ml per 100 g body weight） into the biliopancreatic duct.NAC treated group were given 5% NAC（0.2 ml per 100 g body weight） intraperitoneally 30 min after induction of SAP,NAC＋ ascorbic acid treated group were given 5% NAC＋5% ascorbic acid（0.2 ml per 100 g body weight）intraperitoneally 30 min after induction of SAP.All the animals were sacrificed in 12 h after induction of pancreatitis and acute lung injury.The histopathological changes of lung tissue and wet/dry ratio of lung were evaluated.The levels of malonaldehyde（MDA）,superoxide dismutase（SOD）,reduced glutathione（GSH）,glutathione peroxidase（GSH-PX） in serum,myeloperoxidase（MPO） in the lung,and NF-κB expression in the lung were measured.Results：The histopathological changes of lung tissue,wet/dry ratio of lung,the levels of MDA in serum,the activity of MPO,and the expression of NF-κB in the lung tissue were significantly increased in SAP＋ALI group as compared with those in other three groups（all P0.01）.However,these indices were significantly decreased after the treatment of NAC or NAC＋ascorbic acid（all P0.01）,and were significantly decreased in NAC＋ascorbic acid treated group as compared with NAC treated group.The levels of GSH and GSH-PX in serum were the lowest in SAP＋ALI group（all P0.05）,however,the indices were significantly increased after the treatment of NAC or NAC＋ascorbic acid,especially in NAC treated group（P0.05）,but the two indices were still higher in SO group than the other groups（P0.01）.The levels of SOD had no markedly difference between SAP＋ALI group and NAC treated group（P0.05）,but were higher than in SO group and NAC＋ascorbic acid treated group（P0.01）.Conclusion：NAC and ascorbic acid can restrain activated NF-κB and decrease oxygen free radicals,reduce lung injury and systemic inflammatory response syndrome.NAC and ascorbic acid may have a therapeutic effect on ALI of SAP by removing oxygen free radicals.