Role of Intrapulmonary Expression of Inducible Nitric Oxide Synthase Gene and Nuclear Factor κB Activation in Severe Pancreatitis-associated Lung Injury

摘要

The aim of this study is to explore the relationship of intrapulmonary activation of nuclear factor-κB (NF-κB) and the expression of inducible nitric oxide synthase (iNOS) mRNA with pulmonary injury in rats with severe acute pancreatitis (SAP). Fifty-four Sprague Dawley rats were randomly divided into three groups: sham operation (control) group (n = 18), SAP group (n = 18), and pyrrolindine dithiocarbamate (PDTC) pretreated group (n = 18). A SAP model was induced by retrograde injected 5% sodium taurocholate into the bile-pancreatic duct (1 ml/kg). PDTC-pretreated SAP rats were given 100 mg/kg body weight PDTC intraperitoneally before pancreatitis was induced. Six rats from each group were sacrificed at 3, 6, and 12 h after modeling. Activation of NF-κB in pulmonary tissues and pancreas tissues was detected by immunohistochemical methods. Intrapulmonary expression of iNOSmRNA was assayed by fluorogenic quantitative reverse transcription polymerize chain reaction. The expression of NF-κB in the SAP group in pulmonary tissues was enhanced significantly at any measure point compared with control group (58.4 ± 10.8 vs. 3.8 ± 1.8, 119.8 ± 17.8 vs. 5.2 ± 2.4, and 90.2 ± 14.4 vs. 4.7 ± 2.2, P < 0.01). But the expressions of NF-κB in the PDTC group were significantly lower than those in SAP group (54.3 ± 9.6 vs. 58.4 ± 10.8, 93.9 ± 7.9 vs. 119.8 ± 17.8, and 82.2 ± 13.3 vs. 90.2 ± 14.4, P < 0.05). The number of positive cells in SAP group and PDTC group reached its peak at 6 h and then declined. The expression of iNOSmRNA in PDTC groups was significantly weaker than that in SAP group (2.0 ± 0.8 vs. 2.2 ± 1.9, 2.4 ± 1.2 vs. 4.6 ± 1.8, and 1.5 ± 0.8 vs. 3.2 ± 1.5, P < 0.05). The activation of NF-κB may be involved in the SAP lung injury through regulating the expression of iNOSmRNA. PDTC might inhibit the activation of NF-κB and then reduce the expression of iNOSmRNA and effectively alleviate the severity of lung injury.