雷公藤甲素致小鼠肝损伤对转运体Mrp2和Oatp2的影响

目的：通过多药耐药相关蛋白2（multidrug resistance protein 2，Mrp2）和有机阴离子转运多肽2（organic anion transporting polypeptides 2，Oatp2）初步探究雷公藤甲素诱导小鼠肝损伤的机制。方法：雄性ICR小鼠单次灌胃给予雷公藤甲素（1.0 mg·kg^-1）24 h后称重，摘眼球采血后分离血清，测定血清生化指标；取肝组织做病理切片；采用免疫印迹法检测肝脏组织中Mrp2和Oatp2的蛋白表达量。结果：与对照组相比，雷公藤甲素组肝重指数显著增加（P<0.05），部分血清生化指标显著上升（P<0.05），且肝细胞发生核碎裂和脂肪变性。雷公藤甲素组Oatp2的表达较对照组显著升高了32.79%（P<0.05），而Mrp2的表达较对照组显著下降了45.47%（P<0.01）。结论：雷公藤甲素可能通过上调肝细胞膜转运体Oatp2和下调Mrp2，扰乱肝内胆红素和胆汁酸代谢排泄平衡，可能是雷公藤甲素诱导肝损伤的机制之一。

Effects of triptolide induced liver injury on hepatobiliary membrane transporter Mrp2 and Oatp2

OBJECTIVE To investigate mechanisms of triptolide induced liver injury in mice based on hepatobiliary membrane transporters of multidrug resistance protein 2 (Mrp2) and organic anion transporting polypeptides 2 (Oatp2). METHODS Male ICR mice were randomly divided into two groups:control and triptolide group (n=8). Mice in triptolide group were orally administered with triptolide (1.0 mg·kg^-1) once, while mice in control group were orally administered with 0.5% CMC-Na. Eyeballs were extracted to collect blood and separate serum at 24 h after medication for biochemical analysis. Livers were harvested immediately, a portion of liver was for histological analysis, and the remaining were frozen and stored for Western blot analysis. RESULTS Compared with control group, liver indexes were significantly elevated after triptolide administration. Triptolide treatment significantly increased AST, ALT, ALP, TBIL and IBIL levels compared with control group (P<0.05). Pathological findings of livers in triptolide group showed karyorrhexis and fatty degeneration. Compared with control group, expression of Oatp2 was obviously increased to 32.79% (P<0.05) and Mrp2 was significantly reduced to 45.47% (P<0.01) in triptolide group. CONCLUSION The underlying mechanism of triptolide induced liver injury is related to up-regulation of Oatp2 and down-regulation of Mrp2.