N-乙酰半胱氨酸对大鼠急性胰腺炎肺损伤的治疗保护作用

Protective and therapeutic effects of N-acetylcysteine on lung injury in rats with acute necrotizing pancreatitis

目的探讨急性坏死性胰腺炎(ANP)大鼠肺损伤与肺组织细胞间粘附分子1(ICAM1)、肿瘤坏死因子α(TNFα)mRNA表达的关系及N乙酰半胱氨酸(NAC)对肺损伤的作用。方法26只Wistar大鼠随机分为正常对照、盐水对照、胰腺炎和胰腺炎+NAC四组。以35%牛磺胆酸钠逆行注入胰胆管制作ANP模型,并将NAC(300mg/kg)于造模后1h用于ANP模型,造模后12h取材。采用RTPCR法检测肺组织ICAM1及TNFαmRNA表达,同时观察血脂肪酶、胰腺组织湿/干重比率、肺组织髓过氧化物酶(MPO)及病理改变。结果ANP有肺组织学损伤改变,同时伴有肺组织ICAM1、TNFαmRNA高表达及MPO活力升高。胰腺炎+NAC组与胰腺炎组比较,胰腺湿/干重比率、肺组织ICAM1、TNFαmRNA的表达及MPO均降低。肺组织病理损伤程度与ICAM1、TNFαmRNA表达及MPO均呈正相关,相关系数分别为092、068及092(P<001)。肺MPO与ICAM1、TNFαmRNA表达也呈正相关,相关系数为087及077(P<001)。结论NAC可能通过抑制肺ICAM1、TNFαmRNA的产生及中性粒细胞的聚集,减轻AP所致的肺损伤;对胰腺本身的损伤也可能有一定的保护作用。

Objective To investigate the relationship between the lung injury and expression of ICAM-1 and TNF-α mRNA in rats with acute necrotizing pancreatitis (ANP) and determine protective and therapeutic effects of N-acetylcysteine (NAC) on the lung injury. Methods A total of 26 Wistar rats were randomized into the normal group, normal saline group, ANP group and treated group. The model of ANP was established by retrograde pancreatic injection of sodium taurocholate in the ANP group and the treated group. The rats in the treated group received one intravenous injection of NAC (300 mg/kg) 1 h after taurocholate injection. All the animals were sacrificed in 12 h after induction of pancreatitis. Intrapulmonary ICAM-1 and TNF-α expression was assayed by reverse transcription-PCR. The plasma level of lipase, pancreatic wet/dry weight ratio, histological grading of lung injury and intrapulmonary myeloperoxidase (MPO) level were also determined. Results After induction of ANP, there were alveolar septal thickening and leukocyte infiltration in the lung tissue. Meanwhile, the ICAM-1 and TNF-α mRNA were over-expressed along with the increase in plasma level of lipase and intrapulmonary level of MPO. When NAC was given 1 h after induction of ANP, the intrapulmonary overexpression of the ICAM-1 and TNF-α mRNA was significantly inhibited and the plasma level of lipase and pancreatic wet/dry weight ratio markedly decreased. The score of lung injury after ANP induction was positively correlated to the expression of ICAM-1 and TNF-α mRNA and intrapulmonary level of MPO (r=0.92, 0.68 and 0.92;P<0.01). The intrapulmonary level of MPO was also positively correlated with the expression of the ICAM-1 and TNF-α mRNA (r=0.87 and 0.77;P<0.05). Conclusions The expression of ICAM-1 and TNF-α mRNA and intrapulmonary level of MPO are related to the lung injury after ANP. NAC can reduce lung injury by inhibiting overexperssion of ICAM-1 and TNF-α mRNA and decreasing pulmonary leukocyte infiltration. Meanwhile, it can reduce severity of ANP.