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

Abstract

The aim of this study is to explore the relationship of intrapulmonary activation of nuclear factor-kappaB (NF-kappaB) 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-kappaB 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-kappaB 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-kappaB 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-kappaB may be involved in the SAP lung injury through regulating the expression of iNOSmRNA. PDTC might inhibit the activation of NF-kappaB and then reduce the expression of iNOSmRNA and effectively alleviate the severity of lung injury.

Therapeutic effects of pyrrolidine dithiocarbamate on acute lung injury in rabbits

“…The reason why our data did not show the fully inhibitory effects of PDTC on ALI as others found [19,20] may be due to that PDTC was administered after LPS challenge as the therapeutic process to mimic the situation in clinic. It is also possible that PDTC has different effects between small and large animals, or that the severity of ALI in our model was more serious.…”

Acute lung injury in acute pancreatitis – Awaiting the big leap

“…PDTC treatment further reduced the expression of iNOS mRNA and effectively improved the severity of lung injury. 122,123 Sphingosine-1-phosphate (S1P), a biological active lipid, reduces the NF-kB activation of alveolar macrophages, which leads to prevention of pancreatitis-associated lung injury. 124…”

Niacinamide mitigated the acute lung injury induced by phorbol myristate acetate in isolated rat's lungs

“…PARP was involved in nuclear factor (NF)-κB expression and thereby activated NOS. ADP ribosylaion is required to activate NF-κB-mediated iNOS gene transcription [48,49]. Remick et al [50] also suggested that ADP ribosylation was crucial in the signaling pathway which leads to NOS mRNA expression.…”