Role of intrapulmonary expression of inducible nitric oxide synthase gene and nuclear factor kappaB activation in severe pancreatitis-associated lung injury.
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.
Kan
Shi-hai
SH
Department of Human Anatomy, Binzhou Medical University, No. 346 Guanhai Road, Yantai, 264003, China.
Huang
Fei
F
Tang
Jing
J
Gao
Yun
Y
Yu
Chong-lin
CL
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D055370:Lung Injury / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000150:complications* / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011759:Pyrrolidines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D013859:Thiocarbamates / Q000008:administration & dosage; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism
D015415:Biomarkers; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; C498145:Rela protein, rat; D013859:Thiocarbamates; D051996:Transcription Factor RelA; C020972:pyrrolidine dithiocarbamic acid; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000681:Amylases