抑制NO诱生对BCG免疫性肝损伤中CYP1A2表达的影响

Effect of inducible nitric oxide synthesis inhibitor on CYP1A2 protein expression in BCG-immune liver damage in mice

目的:研究卡介苗(BCG)所致小鼠免疫性肝损伤中,一氧化氮(NO)诱生对肝脏细胞色素P450药物代谢酶系CYP1A2亚型表达的影响. 方法:采用尾静脉注射BCG诱发小鼠产生免疫性肝损伤, HE染色法观察肝脏病理组织学变化,采用免疫组化法测定肝组织诱导型一氧化氮合酶(iNOS)及其CYP1A2的蛋白表达,采用图像梯度灰度扫描法对肝脏病理损伤与iNOS形成进行半定量相关性分析. 结果:尾静脉注射BCG14 d后,可致小鼠肝脏形成大量肉芽肿,iNOS蛋白呈团块状棕色强阳性表达,表达部位与肉芽肿部位相一致,CYP1A2蛋白表达减少;应用选择性iNOS抑制剂氨基胍抑制NO合成,可逆转BCG所致CYP1A2蛋白表达的下调. 结论:BCG免疫刺激条件下,iNOS诱生参与了CYP450药物代谢酶系1A2亚型表达下调机制.

AIM: To study the effect of nitric oxide production on CYP1A2 protein expression in immune liver damage induced by Mycobacterium Calmette-Guerin (BCG) in mice. METHODS: Immune liver damage was induced by intravenous injection of BCG (125 mg/kg) for 2 weeks in vivo. The hepatic tissues injury was estimated by histopatho-logical H-E staining. The protein expression of CYP2E1 and iNOS in hepatic tissues was determined by the method of immunohistochemistry. The correlation between iNOS inducing and liver injury degree was observered by the method of demi-quantification image analysis. RESULTS: Two weeks after of BCG injection, granuloma was easily observed, and over-expression of iNOS protein was detected in the granulomas. The decrease of CYP1A2 protein expression was observed in mice hepatic tissues. Aminoguanidine, a selective iNOS inhibitor, significantly inhibited iNOS protein expression, and reversed down-regulation of CYP1A2 protein induced by BCG-immune liver damage in mice. CONCLUSION: Under the BCG-stimulated condition, nitric oxide production participates in the down-regulation of CYP1A2 protein expression induced by immune hepatic injury in mice.