The role of nitric oxide in lung injury associated with acute necrotizing pancreatitis.
- Author:
Shi CHENG
1
;
Jun ZHAO
;
San-guang HE
;
Mao-min SONG
;
Zhi-hong LI
;
Yue-wei ZHANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Arginine; pharmacology; Disease Models, Animal; Enzyme Inhibitors; pharmacology; Female; Histocytochemistry; Lung; drug effects; metabolism; pathology; Lung Injury; etiology; physiopathology; Macrophages, Alveolar; drug effects; metabolism; pathology; Male; NG-Nitroarginine Methyl Ester; pharmacology; Nitric Oxide; metabolism; physiology; Nitric Oxide Synthase Type II; antagonists & inhibitors; genetics; metabolism; Pancreatitis, Acute Necrotizing; complications; physiopathology; RNA, Messenger; genetics; metabolism; Random Allocation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; genetics; metabolism
- From: Chinese Journal of Surgery 2003;41(5):336-339
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo discuss the role of nitric oxide (NO) in lung injury associated with acute necrotizing pancreatitis (ANP).
METHODSOne hundred and twenty SD rats were randomized into five groups: control group, ANP group, L-arginine (L-arg) pretreatment group, L-NAME pretreatment group, and mixed pretreatment group (n = 24 for each group). Rat ANP model was induced by intraductal administration of 3% sodium taurocholate. Alveolar macrophages (AMs) were obtained by bronchoalveolar lavage. The protein content of bronchoalveolar lavage fluids (BALF), the myeloperoxidase (MPO) of lung tissue and generation of tumor necrosis factor alpha (TNFalpha)and NO by alveolar macrophages were evaluated. The expression of TNFalpha mRNA and iNOS mRNA was also measured.
RESULTSLung injury was aggravated gradually with progression of the disease. The level of MPO of lung tissue and the protein content of BALF showed a steady increase with time and peaked at the 12(th) hour (10.8 +/- 0.6 U/g for MPO and 2,011.0 +/- 105.5 micro g/ml for protein, respectively). TNFalpha and NO secreted by AMs were elevated gradually and peaked at the 6(th) hour (1,624.2 +/- 149.2 pg/ml and 88.8 +/- 6.5 micro mol/L respectively) but decreased at the 12(th) hour. The expression of TNFalpha mRNA and iNOS mRNA was similar with the change of TNFalpha and NO. The parameters of the groups of L-arg, L-NAME and the mixed pretreatment were similar to those of ANP group. The parameters compared with those of the control group showed a significant difference (P < 0.05). The parameters of groups of L-Arg and L-NAME pretreatment in comparison with those of the ANP group showed significant difference (P < 0.05).
CONCLUSIONSOver production of NO mediated by iNOS aggravates lung injury caused by acute necrotizing pancreatitis. Administration of exogenous NOS substrate would worsen lung injury, whereas administration NOS inhibitor would alleviate lung injury.