目的 觀察補骨脂水提物對小鼠的肝毒性及對膽汁酸轉(zhuǎn)運體的影響。方法 補骨脂水提物連續(xù)ig給藥4周, 禁食不禁水12 h, 麻醉動物后取血檢測血清生化, 剖取肝臟稱質(zhì)量并進行肝臟病理組織學檢查。肝臟勻漿后ELISA法檢測膽鹽輸出泵(BSEP)和鈉離子-?；悄懰峁厕D(zhuǎn)運蛋白(NTCP)蛋白的表達情況。結(jié)果 補骨脂水提物以大劑量ig給藥, 連續(xù)給藥2周80 g生藥/kg組小鼠體質(zhì)量顯著降低, 給藥3周3個劑量組小鼠體質(zhì)量均顯著降低。給藥期間, 80 g生藥/kg組小鼠死亡10只, 40 g生藥/kg組小鼠死亡6只。給藥4周結(jié)束補骨脂水提物80 g生藥/kg和40 g生藥/kg組小鼠肝系數(shù)顯著大于對照組。補骨脂水提物80 g生藥/kg組雄性小鼠ALT高于對照組, 雌性小鼠ALP低于對照組, 40 g生藥/kg組雌雄小鼠ALP均低于對照組。補骨脂水提物可使小鼠肝臟出現(xiàn)腫脹變性。補骨脂水提物20 g生藥/kg可導致肝臟BSEP和NTCP均顯著降低。結(jié)論 補骨脂水提物大劑量ig給藥對小鼠肝毒性明顯, 并可影響膽汁酸轉(zhuǎn)運體的表達。

Objective To investigate the hepatoxicity of aqueous extract from Psoralea corylifolia and its effect on bile acid transportation in mice. Methods The aqueous extract from P. corylifolia was given by ig administration for 4 weeks. After fasting for 12 h, mice were anesthetized. The biochemical indices in serum, liver weight, and, histopathological examination were observed. The protein expression of bile saltexport pump (BSEP) and sodium taurocholate cotransporting polypeptide (NTCP) in liver homogenate was detected by ELISA methods. Results The aqueous extract from P. corylifolia in large-doses (80 g crude drug/kg) group was given by ig administration for 2 weeks, the body weight of mice was significantly decreased, continuous ig administration for 3 weeks, the body weight of mice in all three groups was significantly decreased. During the drug administration, ten mice died in 80 g crude drug/kg group and six mice died in 40 g crude drug/kg group. Ig administration for 4 weeks, the liver coefficients of mice in 80 g crude drug/kg group and 40 g crude drug/kg group were significantly larger than those of mice in the control group. In the 80 g crude drug/kg group, the ALT of male mice was higher than that of mice in the control group; The ALP of female mice was lower than that of mice in the control group: In the 40 g/kg group, the ALP of both male and female mice was lower than that of mice in the control group. The aqueous extract from P. corylifolia could make the degeneration of liver swelling of mice. The BSEP and NTCP in liver were significantly decreased in 20 g crude drug/kg group. Conclusion The aqueous extract from P. corylifolia in large dose group could lead the liver injury in mice and influence the expression of bile acid transporter.

重大新藥創(chuàng)制專項項目(2011ZX09201-201-21);國家自然基金項目(81202991)