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目的:应用蛋白质组学技术研究异烟肼致大鼠肝脏损伤时肝脏蛋白质表达谱的变化,为从分子水平上寻找毒性损伤标志物以及阐明异烟肼毒性机制奠定基础。方法:将Wistar大鼠随机分为生理盐水正常对照组和异烟肼组(400 mg.kg-1),分别连续灌胃14 d后处死大鼠,提取肝脏总蛋白,双向凝胶电泳分离蛋白质组成分,采用考马斯亮蓝R-250染色,经ImageMaster2D Platinum5.0软件分析比较两组图谱,并对差异蛋白斑点进行基质辅助激光解吸/电离飞行时间质谱(MALD-TOF-MS)分析鉴定。结果:发现11个差异有统计学意义的蛋白质点,鉴定出8个蛋白,其中,异烟肼处理组比对照组表达升高的蛋白质有鸟氨酸转氨酶、葡萄糖调节蛋白、乙醛脱氢酶和3α-羟甾类脱氢酶,比对照组表达降低的蛋白质有抗氧化酶B166、谷胱苷肽转硫酶、醛铜还原酶和碳酸酐酶。结论:异烟肼可能造成肝脏抗氧化系统和氧化应激异常,这对阐明异烟肼的肝损伤机制具有十分重要的作用。
OBJECTIVE: To study the change of liver protein expression profile induced by isoniazid-induced liver injury in rats by proteomics, and lay a foundation for searching for molecular markers of toxicity and elucidating the mechanism of isoniazid toxicity. Methods: Wistar rats were randomly divided into normal saline control group and isoniazid group (400 mg.kg-1), respectively, after continuous gavage for 14 days, rats were sacrificed, total liver protein was extracted and two-dimensional gel electrophoresis The components were stained with Coomassie Brilliant Blue R-250. The two groups were analyzed by ImageMaster 2D Platinum5.0 software and identified by MALDI-TOF-MS. RESULTS: Eleven differential protein spots were found, and eight proteins were identified. Among them, the isoproterenol dehydrogenase (ORT), ornithine aminotransferase And 3α-hydroxysteroid dehydrogenase. Compared with the control group, the protein with reduced expression had antioxidant enzymes B166, glutathione S-transferase, aldehyde copper reductase and carbonic anhydrase. Conclusion: Isoniazid may cause liver anti-oxidative system and abnormal oxidative stress, which play an important role in elucidating the mechanism of liver injury caused by isoniazid.