淫羊藿苷对大鼠肝药物代谢Ⅱ相酶和药物转运体的影响

Effects of icariin on hepatic phase Ⅱ drug metabolism enzymes and transporters in rats of different age

目的揭示淫羊藿苷(icariin,ICA)对大鼠药物代谢Ⅱ相酶和药物转运体的影响,并比较月龄差异。方法6月龄和18月龄SD雄性大鼠随机分为6月龄大鼠生理盐水组(6NS)和ICA组(6ICA),18月龄大鼠生理盐水组(18NS)和ICA组(18ICA),每组8只,灌胃ICA(60 mg.kg-1)4 w后取肝脏,钙沉淀法提取肝微粒体,BCA法测定微粒体蛋白浓度。比色法测定谷胱甘肽-S-转移酶(glutathione S-transferase,GSTs)活性;紫外分光光度法测定尿苷-5'-二磷酸葡醛酰转移酶(uridine 5'-diphosphate glucuronosyl transferase,UGTs)活性;ELISA法测定有机阴离子转运多肽2(organic anion transporting polypeptide 2,Oatp2)和有机阴离子转运体2(organic anion transporter2,OAT2)含量;Real-Time RT-PCR检测UGT1A6、UGT2B7、GST-π、OAT2和Oatp2 mRNA表达。结果 ICA(60mg.kg-1)明显增加Oatp2和OAT2含量,上调OAT2和Oatp2 mRNA的表达,但未见明显月龄差异;对GSTs和UGTs活性以及UGT1A6、UGT2B7、GST-πmRNA的表达未见明显影响。结论 ICA对大鼠肝组织OAT2和Oatp2具有诱导作用,该作用未见明显月龄差异,对GSTs和UGTs无明显影响。

Objective To compare the effects and difference of icariin on hepatic phase Ⅱdrug metabolism enzymes and transporters in rats different age.Methods Six-month-old and eighteen-month-old SD male rats were randomly divided into control group and icariin group.After intragastric administration of icariin（60 mg·kg-1） for 4 weeks,hepatic microsomes were extracted by calcium precipitation method.The activities of glutathione S-transferase（GSTs） and uridine 5＇-diphosphate glucuronosyl transferase（UGTs） were detected colorimetrically.ELISA was used to determined the contents of organic anion transporting polypeptide 2（Oatp2） and organic anion transporter 2（OAT2）.Expressions of UGT1A6,UGT2B7,GST-π,OAT2 and Oatp2 mRNA were analyzed by real time RT-PCR.Results Compared with control group,the contents of Oatp2 and OAT2 and the expressions of Oatp2 and OAT2 mRNA were increased remarkably by icariin.There was no significant difference of changes mentioned above between six-month-old and eighteen-month-old rats.The activities of UGTs and GSTs and expressions of UGT1A6,UGT2B7 and GST-π mRNA were unchanged.Conclusion Icariin（60 mg·kg-1） could induce Oatp2 and OAT2 expression,but no age-difference was shown.