|
诱导型一氧化氮合酶选择性抑制剂对大鼠免疫性肝损伤的影响 |
| |
章国良 林志彬 张波
【摘要】 目的 探讨大鼠免疫性肝损伤模型中一氧化氮(NO)的作用及诱生规律，诱导型一氧化氮合酶(iNOS)选择性抑制剂的作用机制。方法 采用原位PCR法对免疫损伤性肝细胞NOS基因表达进行原位检测，并观察细胞培养上清中NO生成量及乳酸脱氢酶(LDH)活性的变化。结果 用卡介苗(BCG，15、30、50 mg/只静脉注射)单独投与或与炎性细胞因子配伍（CM，含白细胞介素1β，干扰素γ，肿瘤坏死因子α及细菌脂多糖）可引起培养上清NO浓度及LDH活性明显升高(均P<0.05)，NO生成量与肝损伤程度成正比，而与BCG剂量成反比；大鼠免疫损伤性肝实质细胞NOS基因表达以可溶性胞浆型iNOS为主；iNOS选择性抑制剂氨基胍在明显抑制细胞培养上清中NO生成(83.4%，P<0.05)的同时，减轻肝细胞损伤的程度(36.0%，P<0.05)；而转录抑制剂放线菌素D则加重肝损伤(增加25.5%，P<0.05)。结论 在免疫刺激条件下诱导生成的NO主要参与肝损伤机制。
【关键词】 肝疾病 一氧化氮 酶抑制剂
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
【Abstract】 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 stimu[1] [2] [3] 下一页
上一个医学论文： 低氧对大鼠不同节段肺动脉一氧化氮合酶mRNA表达的影响
下一个医学论文： 131碘
|
|
|
|
|
|
|
您现在的位置： 绿色健康网 >> 医学论文 >> 临床医学论文 >> 正文