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

作者	单位
洪振丰	福建中医学院
李天骄	福建中医学院
赵锦燕	福建中西医结合研究院
林久茂	福建中西医结合研究院
周建衡	福建中医学院
胡娟	福建中医学院

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中文摘要:

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。

英文摘要:

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 alanine 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.

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