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目的研究四氯化碳、醋氨酚、半乳糖胺诱发大鼠急性肝炎时肝脏微粒体中HP450及CytP450的变化。方法采用[3H]mepyramine为放射性配体,利用受体-配体结合技术检测HP450,用差示光谱法检测CytP450,同时采用荧光法检测外周血液中组织胺水平。结果在3种肝毒剂诱发大鼠发生急性肝炎时,大量肝脏微粒体中HP450的水平显著降低,大鼠肝脏微粒体中的CytP450含量也明显下降,HP450和CytP450的降低具有一致性,此外还发现急性肝炎动物血清中的组织胺水平明显高于正常组(P<0.01)。结论大鼠肝脏微粒体中HP450的水平在急性肝炎中显著降低,可能与受体的“下行调节”及肝毒物质降低CytP450有关,检测人体肝脏组织中HP450水平、外周血中HP450的酶促反应中间代谢物、代谢终产物,是否可作为判断人体急性肝炎时肝脏损害程度的一个特异性指标,值得进一步研究与探讨。
Objective To study the changes of HP450 and CytP450 in liver microsomes induced by carbon tetrachloride, acetaminophen and galactosamine in acute hepatitis. Methods [3H] mepyramine was used as radioligand. HP450 was detected by receptor-ligand binding assay. CytP450 was detected by differential spectroscopy. Histamine level in peripheral blood was detected by fluorometry. Results When acute hepatitis was induced by 3 kinds of hepatotoxic agents, the levels of HP450 in a large number of liver microsomes were significantly decreased, the contents of CytP450 in liver microsomes were significantly decreased, and the reductions in HP450 and CytP450 were also found. In addition, Histamine levels in acute hepatitis animal serum were significantly higher than those in the normal group (P <0.01). Conclusions The level of HP450 in rat liver microsomes is significantly decreased in acute hepatitis, which may be related to the “downregulation” of the receptors and the reduction of CytP450 by hepatic toxicants. The level of HP450 in human liver tissue and the level of HP450 in peripheral blood Intermediate metabolites and metabolic end products, whether as a specific index to judge the extent of liver damage in acute hepatitis, deserve further study and discussion.