粗叶悬钩子总生物碱对急性肝损伤大鼠肝组织CYP2E1与CYP3A1酶mRNA表达的影响

Effect of Total Alkaloids of Rubus alceaefolius Poiron on Gene Expressions of CYP2E1 and CYP3A1 in Rats with Acute Liver Injury

目的研究粗叶悬钩子总生物碱对肝药物代谢酶CYP2E1和CYP3A1 mRNA表达的影响。方法60只SD大鼠随机分为正常组、模型组、联苯(对照)组和粗叶悬钩子总生物碱低、中、高剂量组,采用CCl4腹腔内注射建立急性肝损伤大鼠模型,检测各组血清谷丙转氨酶(ALT)、谷草转氨酶(AST)及肝组织病理损伤程度,RT-PCR检测各组肝组织中CYP2E1、CYP3A1 mRNA的表达水平。结果粗叶悬钩子总生物碱中、高剂量组大鼠血清中ALT、AST显著降低(P<0.01),低剂量组ALT显著降低(P<0.01),AST降低差异无统计学意义(P>0.05);各剂量组大鼠肝损伤程度显著减轻(P<0.01);肝组织中CYP2E1、CYP3A1 mRNA表达均显著降低(P<0.05,P<0.01)。结论粗叶悬钩子总生物碱能明显降低ALT、AST含量,保护肝细胞损伤,抑制肝组织中CYP2E1、CYP3A1 mRNA的表达。

Objective To explore the effects of total alkaloids of Rubus alceaefolius Poiron （RAP） on gene expressions of drug-metabolic enzymes, CYP2E1 and CYP3A1 in liver. Methods Sixty SD rats were randomly divided into six groups （ 10 rats in each）, the blank control group, the model control group, the biphendate group and the three RAP treated groups treated respectively with low-, middle- and high-dose of RAP. The model of acute hepatic injury was established with intra-peritoneal injection of carbon tetrachloride. Serum levels of ala- nine aminotransferase （ALT） and aspartate aminotransferase （AST）, and severity of hepatic tissue injury were measured, and the mRNA expressions of CYP2E1 and CYP3A1 in liver tissue were detected by RT-PCR. Results As compared with the model group, serum levels of ALT and AST were significantly lower in the high- and middle-dose ARP group （ P 〈0. 01 ）, but in the low-dose group, only ALT was significantly lower （ P 〈0. 01 ） ; the Severity of liver injury was milder in the RAP groups （ P 〈0.01 ） ; and both CYP2E1 and CYP3A1 mRNA expressions in liver were significantly lower in the biphendate and all RAP treated groups （ P〈0.01 or P〈0.05）. Conclusion RAP could significantly reduce the ALT and AST levels, protect liver cells from injury, and inhibit the mRNA expressions of CYP2E1 and CYP3A1 in liver tissue.