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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 NAC combined with ascorbic acid on acute lung injury (ALI) in rats with severe acute pancreatitis (SAP). Methods: Forty SD rats were randomly divided into sham operation (SO) group, SAP + ALI group, NAC treatment group and NAC + ascorbate treatment group. The SAP + ALI model was induced by retrograde injection of 4% sodium taurocholate (0.1ml / 100g) into the pancreaticobiliary duct. The NAC treated group was injected intraperitoneally with 5% NAC (0.2ml / 100g) and NAC + ascorbate group 5% NAC (0.2 ml / 100 g) + 5% ascorbic acid (0.2 ml / 100 g) was injected intraperitoneally 30 min after modeling. The rats were sacrificed at 12 hours after the model was established. The pathological changes of the lung tissue, the wet / dry weight ratio of the lung tissue, the contents of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) (GSH-PX), myeloperoxidase (MPO) and nuclear factor-kappa B (NF-κB) in lung tissue. Results: Compared with the other three groups (P <0.01), the indexes of wet / dry weight, the pathological damage of lung tissue, the contents of MDA, MPO and NF-κB in the SAP + ALI group were significantly higher than those in the NAC group or the NAC + ascorbate group (P <0.01), and the NAC + ascorbic acid treatment group was significantly lower than the NAC treatment group (P <0.01), but higher than the SO group (P <0.01); GSH and GSH-PX in the SAP + ALI group was significantly lower than the other three groups (P <0.05), NAC or NAC + ascorbic acid treatment significantly increased these indicators, and NAC + ascorbate treatment group was significantly higher than the NAC treatment group (P <0.05), but were lower than the SO group (P <0.01). There was no significant difference between SOD + ALI group and NAC group (P> 0.05), but both of them were lower than SO group and NAC + ascorbate group (P <0.01). Conclusion: NAC and ascorbic acid can inhibit the activation of NF-κB and reduce the production of oxygen free radicals, thereby reducing the lung injury and systemic inflammatory response syndrome (SIRS) in patients with severe acute pancreatitis, acute lung injury in severe acute pancreatitis Injury has important therapeutic and protective effects.