抗组胺药敏感性细胞色素P450在大鼠肝硬化中的变化

The variance of anti histaminergic drug sensitive cytochrome P450 in cirrhotic rats

目的研究四氯化碳诱导大鼠肝硬化的不同时期肝脏微粒体中抗组胺药敏感性细胞色素Ｐ４５０（ＨＰ４５０）及血液中组胺水平的变化趋势。方法采用３Ｈｍｅｐｙｒａｍｉｎｅ为放射性配体，利用受体配体结合研究技术检测ＨＰ４５０，同时采用荧光法检测外周血液中组胺水平。结果在肝硬化早期，大鼠肝脏微粒体中ＨＰ４５０的水平降低明显，在肝硬化中期和晚期，ＨＰ４５０水平的降低逐渐达到一最低水平的稳定值。ＨＰ４５０的内在亲和力也随之改变，早期Ｋｄ值明显下降，受体的亲和力升高，然后随着病变的发展，Ｋｄ值逐渐升高，即受体的亲和力逐渐下降，但各期Ｋｄ值经统计学检验后差异无显著性（与对照组相比Ｐ＞０．０５）。动物血液中的组胺水平早期明显升高，到了中期和晚期后组胺下降的幅度逐渐减低。结论组胺水平在肝硬化大鼠体内升高显著，可能对肝硬化的形成起着重要的作用。

Objective To observe the changes of anti histaminergic drug sensitive cytochrome P450 (HP450) in CCl 4 induced cirrhosis in rats. Methods Using 3H mepyramine as radioactive ligand, the variance of HP450 was studied by means of receptor ligand binding assay. Meanwhile fluorescence technique was used to check the changes of histamine in peripheral blood of CCl 4 induced cirrhosis. Results Both the HP450 and histamine in different stages of cirrhosis were significantly higher than cirrhotic at the early stage, and were significantly decreased more than that at the medium and later stages. The Kd value and the concentration of HP450 and histamine tended to keep at a steady level. Conclusion The levels of histamine and HP450 may play an important role in cirrhosis and the possible mechanism of low HP450 in cirrhosis might be concerned with the “down regulation” of histamine receptor.