目的 研究補(bǔ)骨脂不同提取部位大鼠長(zhǎng)期ig給藥的毒性反應(yīng)。方法 按照一定的方法制備得到補(bǔ)骨脂不同部位提取物，即滲漉藥渣、上層滲漉液和混合物。將SD大鼠98只，按體質(zhì)量、性別隨機(jī)分為7組，即對(duì)照組，補(bǔ)骨脂藥渣高、低劑量組，補(bǔ)骨脂干膏高、低劑量組，補(bǔ)骨脂混合物高、低劑量組（高、低劑量均相當(dāng)于生藥6、3 g/kg），每組14只。以1 mL/100 g劑量ig給藥12周。每周稱大鼠體質(zhì)量，給藥結(jié)束后，剖取臟器，計(jì)算臟器系數(shù)；取血，檢測(cè)血清生化指標(biāo)；取肝臟和腎臟組織進(jìn)行組織病理學(xué)檢查。結(jié)果 連續(xù)給藥12周后，與對(duì)照組相比，混合物高劑量組以及干膏高劑量組雄性大鼠體質(zhì)量顯著降低（P<0.05、0.01）；與對(duì)照組相比，隨給藥時(shí)間的延長(zhǎng)，干膏低劑量組雌性大鼠體質(zhì)量顯著降低（P<0.05），其余給藥組無(wú)顯著差異。除干膏高、低劑量組外，其余各組雄性、雌性大鼠肝臟系數(shù)均顯著高于對(duì)照組（P<0.01、0.001）。與對(duì)照組比較，雄性大鼠混合物高劑量組以及藥渣高、低劑量組的丙氨酸氨基轉(zhuǎn)換酶（ALT）、三酰甘油（TG）顯著下降（P<0.05、0.01），混合高劑量組和干膏高、低劑量組尿素氨（BUN）顯著降低（P<0.05、0.01、0.001）。與對(duì)照組相比，雌性大鼠混合物高劑量組和干膏高劑量組總膽汁酸（TBA）顯著升高（P<0.01），混合物高劑量組和藥渣高、低劑量組總膽紅素（TBIL）顯著升高（P<0.05、0.01）。結(jié)論 大鼠長(zhǎng)期ig給予補(bǔ)骨脂不同提取物可造成一定的毒性反應(yīng)，且具有一定的劑量相關(guān)性，主要表現(xiàn)為肝臟和腎臟功能損害，并且損傷程度存在雌雄差異。

Objective To study the toxicity of different extracts of Psoralea corylifolia by long-term ig administration in rats. Methods The extracts from different parts of Psoralea corylifolia were prepared by a certain method, namely, osmotic residue, superficial osmotic solution, and mixture. 98 SD rats were randomly divided into 7 groups according to body weight and sex, namely, control group, high and low dose group of Psoralea corylifolia residue, high and low dose group of Psoralea corylifolia dry ointment, and high and low dose group of Psoralea corylifolia mixture (high and low doses were equivalent to 6, 3 g/kg of crude drugs), and each group had 14 rats. 1 mL/100 g was ig administered for 12 weeks. The weight of the rats were weighed every week. After treatment, the organs were dissected and the organ coefficients were calculated, the serum biochemical indicators was separately measured. And liver and kidney tissues were taken for histopathological examination. Results After 12 weeks of continuous administration, compared with control group, the body weight of male rats in the high-dose group of mixture and highdose group of dry ointment decreased significantly (P<0.05, 0.01), compared with the control group, the body weight of female rats in the low-dose group of dry ointment decreased significantly with the prolongation of administration time (P<0.05), while there was no significant difference in the other groups. In addition to the high and low dose groups of dry ointment, the liver coefficients of the female and male rats in the other extract groups were significantly higher than those in the control group (P<0.01, 0.001). Compared with the control group, the ALT and TG of male rats were significantly decreased in the high-dose group of mixture, and the high and low dose group of residue (P<0.05, 0.01), and the BUN were significantly decreased in the high-dose group of mixture and the high and low dose groups of dry ointment (P<0.05, 0.01, 0.001). Compared with the control group, TBA of female rats was increased significantly in the high-dose group of mixture and the high-dose group of dry ointment (P<0.01), TBRL was increased significantly in the high-dose group of mixture and the high and low-dose group of residue (P<0.05, 0.01).Conclusion Long-term ig administration of different extracts of Psoralea corylifolia can cause certain toxicity in rats, and it has a dose-dependent effect. The main manifestations are liver and kidney function damage, and the degree of damage is different between male and female.

國(guó)家自然科學(xué)基金（81673826，81703790）；國(guó)家重大新藥創(chuàng)制專項(xiàng)（2014ZX09304307-001-005）