大黄素对大鼠血清肝功能、肝脏转运蛋白及代谢酶UGT1A1表达的影响  

Effects of emodin on serum liver function, liver transporter and metabolic enzyme UGT1A1 expression in rats

作　　者：韦美金 黄娟[1,2] 白俊其 蔡锡潮[1,2] 丘小惠[1,2] WEI Mei-jin;HUANG Juan;BAI Jun-qi;CAI Xi-chao;QIU Xiao-hui(Second Clinical College of Guangzhou University of Chinese Medicine,Guangzhou Guangdong 510006,China;Guangdong Province Academy of Traditional Chinese Medicine,Guangzhou Guangdong 510120,China)

机构地区：[1]广州中医药大学第二临床医学院,广东广州510006 [2]广东省中医院,广东广州510120

出　　处：《时珍国医国药》2018年第7期1551-1555,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81373967);广东省中医药局科研项目(20162056)

摘　　要：目的研究长期灌胃给予大黄素对大鼠血清肝功能、肝脏转运蛋白及代谢酶UGT1A1表达的影响,探讨大黄素肝毒性作用机制。方法将大鼠随机分为空白组、大黄素低剂量组(20 mg·kg^(-1)·d^(-1))、中剂量组(40 mg·kg^(-1)·d^(-1))及高剂量组(80 mg·kg^(-1)·d^(-1)),灌胃30 d后,检测大鼠血清中的谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆红素(TBIL)、直接胆红素(DBIL)、总胆汁酸(TBA)水平。采用实时荧光定量RT-PCR测定大鼠肝脏中转运蛋白P-gp、Mrp2、Mrp3、Oatp1、Oatp2、Bsep、Ntcp及代谢酶UGT1A1的mRNA表达,以Western blot方法测定大鼠肝脏中P-gp、Mrp3、Ntcp及UGT1A1的蛋白表达。结果中剂量组及高剂量组大鼠血清ALP、TBIL、DBIL、TBA明显升高(P<0.05或P<0.01),肝脏P-gp、Mrp3 mRNA及蛋白表达均显著上调(P<0.01);而肝脏中Ntcp及UGT1A1 mRNA及蛋白表达显著下调(P<0.05或P<0.01)。结论长期给予较高剂量的大黄素有肝脏毒性的风险。大黄素致肝毒性可能与肝脏中P-gp、Mrp3表达的上调、Ntcp及UGT1A1表达的下调有关。Objective To study the effect of emodin on the liver-associated in serum,liver transporter and metabolic enzyme UGT1 A1 in rats,and to explore the mechanism of emodin in hepatotoxicity. Methods Rats were randomly divided into blank group,low emodin group（ 20 mg·kg^-·d^-1）,medium dose group（ 40 mg·kg^-·d^-1） and high dose group（ 80 mg·kg^-·d^-1）,After 30 days of administration,detecting the level of Alanine aminotransferase（ ALT）,aspartate transaminase（ AST）,alkaline phosphatase（ ALP）,total bilirubin（ TBIL）,direct bilirubin（ DBIL）,total bile acid（ TBA）. The expression of P-gp,Mrp2,Mrp3,Oatp1,Oatp2,Bsep,Ntcp and UGT1 A1 mRNA were detected by real-time quantitative RT-PCR. Western blot was used to deternmine the expression of P-gp,Mrp3,Ntcp and UGT1 A1. Results The levels of ALP,TBIL,DBIL and TBA in the middle and high dose groups were significantly increased（ P 0. 05 or P 0. 01）. The levels of P-gp,Mrp3 mRNA and protein in the liver were significantly up-regulated（ P 0. 01）. The levels of Ntcp and UGT1 A1 mRNA and protein were significantly down-regulated（ P 0. 05 or P 0. 01）. Conclusion Long-term administration of higher doses of emodin lead to liver toxicity. Emodin hepatotoxicity may be related to up-regulation of P-gp,Mrp3 expression in liver,down-regulation of Ntcp and UGT1 A1 expression.

关 键 词：大黄素 肝毒性 肝功能 转运蛋白 UGT1A1 

分 类 号：R285.5[医药卫生—中药学]