钝化NF-κB的活化对酒精性肝损伤大鼠CYP3A的影响  

Blunted the increased hepatic nuclear factor-κB activity can influence hepatic CYP3A metabolism activity

作　　者：康晓琳[1] 薛永志[1] 许秀举[2] 刘和莉[1] 

机构地区：[1]包头医学院药理学教研室,内蒙古包头014060 [2]包头医学院营养与食品卫生教研室,内蒙古包头014060

出　　处：《中国药理学通报》2010年第9期1216-1219,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30760289);内蒙古自然科学基金资助项目(No2009MS1104);内蒙古教育厅资助项目(NoNJ03148)

摘　　要：目的研究核转录因子-κB(nuclear fastor kappa B,NF-κB)在酒精性肝损伤大鼠模型中的作用及对细胞色素P4503A(cytochrome P450 3A,CYP3A)代谢活力的影响。方法采用白酒灌胃法复制大鼠酒精性肝损伤模型,肝脏组织HE染色和血清中ALT和AST水平测定观测大鼠肝损伤情况,采用免疫组化法检测肝脏NF-κB的蛋白表达,通过HPLC法检测CYP3A的探针药物咪哒唑仑的血浆药物浓度,采用热板法观察大鼠舔足反应来体现咪哒唑仑的代谢情况,从而反映咪哒唑仑特异性代谢酶CYP3A的代谢活力。结果酒精性肝损伤模型组表现为轻度脂肪变性和炎症坏死,NF-κB明显活化,CYP3A代谢活力增强(P<0.05);钝化NF-κB的活化后,肝脏脂肪变性程度明显减轻,CYP3A代谢活力下调(P<0.05)。结论钝化NF-κB活化,可以减轻酒精性肝损伤的程度,并下调酒精性肝损伤导致的CYP3A代谢活性的增强。Aim To determine the action of nuclear factor kappa B（NF-κB） in alcoholic liver injury and how to influence catalytic activity of hepatic cytochrome P450 3A（CYP3A）.Methods The models of alcoholic liver injury in Wistar rats were established by feeding with ethanol or salazosulfapyridine（SASP） for 20 days.The liver histopathology was revealed by hematoxylin and eosin（HE） method and serum concentration of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）.The expression of NF-κB protein was detected by immunohistochemistry method.The serum concentration of midazolam（MDZ） was measured by high-performance liquid chromatography（HPLC） method and the during of licking when heat stimulation of foot.The CYP3A catalytic activity was reflected by these methods.Results The liver histopathology in ethanol group revealed mild to moderate steatosis and mild necroinflammation.Hepatic NF-κB expression increased significantly in ethanol-treated group when compared with control.Ethanol treatment significantly elevated hepatic CYP3A metabolism activity（P 0.05）.Inhibiting NF-κB prevented ethanol-induced hepatotoxicity and inhibited the development of a fatty liver,decreasing the elevation of hepatic CYP3A metabolism activity and reducing hepatic NF-κB expression（P 0.05）.Conclusion Blunted NF-κB activation improves liver histopathology and recoveries the up-regulation of hepatic CYP3A metabolism activity in ethanol-induced liver injury rats.

关 键 词：酒精性肝损伤 NF-ΚB CYP3A 咪达唑仑 大鼠 高效液相色谱 

分 类 号：R-332[医药卫生] R322.47