[Effects of selective induceble nitric oxide synthase inhibitor on immunological hepatic injury in rat].
OBJECTIVE
To investigate the role and induced regulation of nitric oxide (NO) in rat immunological hepatic injury, and the effect of selective inhibitor on induceble nitric oxide synthase (iNOS).


METHODS
The intracellular NOS gene expression in the immune damaged hepatocytes was determined by in situ PCR technique, and NO concentration and lactate dehydrogenase (LDH) activity in culture supernatant were measured.


RESULTS
Administration of bacille calmette guerin (BCG, 15, 30, 50 mg/rat, i.v.) alone or BCG with the inflammatory cytokines mixture (CM), including IL-1 beta, IFN-gamma, TNF-alpha and lipopolysacchride (LPS) significantly increased NO production and LDH release in culture medium(P < 0.05). NO production was enhanced with hepatic injury degree in direct proportion, and with BCG dose in inverse proportion. Under immunological stimuli condition, hepatocytes NOS mRNA mainly expressed an induceble and soluble isoform (iNOS) in cytoplasm. Aminoguanidine (AG), a selective iNOS inhibitor, inhibited NO production and LDH release (83.4% and 36.0%, P < 0.05), but the transcription inhibitor actinomycin D enhanced LDH level in the medium (25.5%, P < 0.05).


CONCLUSIONS
NO produced by immunological stimuli participates in rat hepatic injury mechanism.
Department of Pharmacology, Beijing Medical University.
G
G
Zhang
Z
Z
Lin
B
B
Zhang
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides; D008107:Liver Diseases / Q000201:enzymology*; D008297:Male; D009163:Mycobacterium bovis; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat