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Effects of selective induceble nitric oxide synthase inhibitor on immunological hepatic injury in rat

Zhang Guoliang, Lin Zhibin, Zhang Bo. Department of Pharmacology , Beijing Medical University, Beijing 100083  
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, 15,30,50mg/rat, iv) alone or BCG with the inflammatory cytokines mixture (CM), including IL 1β, IFN γ, TNF α 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). Conclusion NO produced by immunological stimuli participates in rat hepatic injury mechanism.
【Fund】: 国家自然科学基金
【CateGory Index】: R575.1
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